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1. RESOLUTE Trial Aims to Investigate the Value of Adding Local Ablative Treatment to Standard Systemic Treatment for Unresectable Oligometastatic Colorectal Cancer (RESOLUTE)

Author: Walter and Eliza Hall Institute of Medical Research and Cancer Council Victoria
Published: 2023

2. Laparoscopic Approach to Cancer of the Endometrium

Author: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Tyco Healthcare Group, Gynetech, Queensland Government - Smart Health Research Grant, National Health and Medical Research Council, Australia, Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council Western Australia, and Cancer Australia
Published: 2019

3. Use of Shade in U.S. and Australian City Parks (Shade)

Author: Cancer Council Victoria
Published: 2017

4. Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses

Author: University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., Camp, Nicola J., University of Michigan ICPCG Group ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, University of Michigan ICPCG Group ; University of Michigan, Ann Arbor, Michigan, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah ; Division of Genetic Epidemiology, University of Utah School of Medicine, 391, Chipeta Way, Suite D, Salt Lake City, UT 84108., African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Fox Chase Cancer Center, Philadelphia, Pennsylvania, African American Hereditary Prostate Cancer ICPCG Group ; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, African American Hereditary Prostate Cancer ICPCG Group ; National Human Genome Research Institute, NIH, Bethesda, Maryland, African American Hereditary Prostate Cancer ICPCG Group ; Translational Genomics Research Institute, Genetic Basis of Human Disease Research Division, Phoenix, Arizona, ACTANE Consortium ICPCG Group ; Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia, ACTANE Consortium ICPCG Group ; Department of Oncology, McGill University, Montreal, Quebec, Canada, ACTANE Consortium ICPCG Group ; The Norwegian Radium Hospital, Oslo, Norway, ACTANE Consortium ICPCG Group ; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey, UK, ACTANE Consortium ICPCG Group ; Cancer Research UK Genetic Epidemiology Unit, Cambridge, UK, ACTANE Consortium ICPCG Group ; Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington, BC/CA/HI ICPCG Group ; Department of Health Research and Policy, Stanford School of Medicine, Stanford, California ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Stanford Comprehensive Cancer Center, Stanford School of Medicine, Stanford, California, BC/CA/HI ICPCG Group ; Department of Urology and Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California, Data Coordinating Center for the ICPCG and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, FHCRC ICPCG Group ; Fred Hutchinson Cancer Research Center, Divisions of Public Health Sciences, Seattle, Washington, FHCRC ICPCG Group ; Cancer Genetics Branch, National Institutes of Health, Bethesda, Maryland, FHCRC ICPCG Group ; Institute for Systems Biology, Seattle, Washington, Johns Hopkins University ICPCG Group and Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, Mayo Clinic ICPCG Group and Mayo Clinic, Rochester, Minnesota, University of Tampere ICPCG Group, University of Tampere and Tampere University Hospital, Tampere, Finland, University of Ulm ICPCG Group ; Department of Urology, University of Ulm, Ulm, Germany, University of Ulm ICPCG Group ; Institute of Human Genetics, University of Ulm, Ulm, Germany, University of Ume?? ICPCG Group ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, University of Ume?? ICPCG Group ; Oncologic Centre, Ume?? University, Ume??, Sweden, University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, Christensen, G. Bryce, Baffoe-Bonnie, Agnes B., George, Asha, Powell, Isaac, Bailey-Wilson, Joan E., Carpten, John D., Giles, Graham G., Hopper, John L., Severi, Gianluca, English, Dallas R., Foulkes, William D., Maehle, Lovise, Moller, Pal, Eeles, Ros, Easton, Douglas, Badzioch, Michael D., Whittemore, Alice S., Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Xu, Jianfeng, Stanford, Janet L., Johanneson, Bo, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A., Wiley, Kathleen E., Isaacs, Sarah D., Walsh, Patrick C., Isaacs, William B., Thibodeau, Stephen N., McDonnell, Shannon K., Hebbring, Scott, Schaid, Daniel J., Lange, Ethan M., Cooney, Kathleen A., Tammela, Teuvo L. J., Schleutker, Johanna, Paiss, Thomas, Maier, Christiane, Gr??nberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Farnham, James M., Cannon-Albright, Lisa A., and Camp, Nicola J.
Abstract: BACKGROUND Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11???q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9???cM. CONCLUSIONS Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate 70: 735???744, 2010. ?? 2010 Wiley-Liss, Inc.
Published: 2010

5. Trends in Recall and Appraisal of Anti-Smoking Advertising Among American Youth: National Survey Results, 1997???2001

Author: University of Michigan, Ann Arbor, Michigan, University of Michigan, Ann Arbor, Michigan; Institute for Social Research, University of Michigan, PO Box 1248, Ann Arbor, Michigan, 48106-1248, Center for Behavioral Research in Cancer, The Cancer Council Victoria, Carlton, Victoria, 3053, Australia, Ann Arbor, Johnston, Lloyd D., Terry-McElrath, Yvonne M., O???malley, Patrick M., Wakefield, Melanie, University of Michigan, Ann Arbor, Michigan, University of Michigan, Ann Arbor, Michigan; Institute for Social Research, University of Michigan, PO Box 1248, Ann Arbor, Michigan, 48106-1248, Center for Behavioral Research in Cancer, The Cancer Council Victoria, Carlton, Victoria, 3053, Australia, Ann Arbor, Johnston, Lloyd D., Terry-McElrath, Yvonne M., O???malley, Patrick M., and Wakefield, Melanie
Abstract: Public health efforts to reduce the harms related to tobacco use currently include a significant emphasis on anti-smoking media campaigns. This paper provides (a) data on the overall extent of exposure to anti-smoking media among American youth from 1997 to 2001, (b) an appraisal of general youth reactions to such advertising, and (c) an examination of how exposure levels and reactions vary by socio-demographic characteristics. Data were obtained from the Monitoring the Future study, an ongoing nationwide study of youth. Data were collected each year from nationally representative separate and nonoverlapping school samples of 8th, 10th, and 12th grade students ( N = 29,724; 24,639; and 12,138, respectively). Self-reported levels of recalled exposure to both electronic and print anti-smoking advertising were measured, as well as the judged impact and perceived exaggeration of such advertising. Data indicate that significant increases in overall exposure to anti-smoking advertising occurred over the study time period. These increases were associated with (a) increases in the self-reported likelihood that anti-smoking advertising diminished the probability of individual smoking behaviors, and (b) increases in the perceived level to which anti-smoking advertising exaggerates the risks associated with smoking. Further, these trends were significantly associated with various characteristics???most notably, ethnicity, smoking behaviors, and residence in a state with an ongoing tobacco-control program having a media component.
Published: 2006

6. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Author: Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. 2Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. 5Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain. 6IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. 7Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 8Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. 9Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain. 10Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Institut de Recerca (VHIR), and Universitat Autonoma de Barcelona, Barcelona, Spain. 11Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 12Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece. 13Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain. 14Medical Oncology Service, Hospital Clínico Lozano Blesa, San Juan Bosco, Zaragoza, Spain. 15Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada. 16Department of Oncology, Lund University, Lund, Sweden. 17Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. 18Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 19Department of Oncology, Lund University Hospital, Lund, Sweden. 20Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. 21Center for Clinical Cancer Genet, Osorio, Ana, Milne, Roger L, Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco, Ignacio, de la Hoya, Miguel, Duran, Mercedes, Díez, Orland, Mai, Phuong L, Neuhausen, Susan L, Lejbkowicz, Flavio, Ottini, Laura, Lee, Andrew, Buys, Saundra S, Thomassen, Mads, Zaffaroni, Daniela, Andrulis, Irene, Benitez, Javier, Schmutzler, Rita Katharina, Eccles, Diana, Swe-Brca, Platte, Radka, Hodgson, Shirley, Tischkowitz, Marc, Meindl, Alfons, van Deurzen, Carolien H M, Nathanson, Katherine, Donaldson, Alan, Varon-Mateeva, Raymonda, Teulé, Alex, Walsh, Christine, Poppe, Bruce, Ditsch, Nina, Arver, Brita, Morrison, Patrick, Plendl, Hans Jörg, Sutter, Christian, Rantala, Johanna, Johannsson, Oskar Th, Janavicius, Ramunas, Wappenschmidt, Barbara, Stoppa-Lyonnet, Dominique, Brewster, Wendy, Olswold, Curtis, Ding, Yuan Chun, Rookus, Matti A, Lester, Jenny, John, Esther M, Gehrig, Andrea, Herzog, Josef, Lalloo, Fiona, Kauff, Noah, Whittemore, Alice S, Rau-Murthy, Rohini, Weeman, Kisa, Claes, Kathleen, Rutherford, Thomas, Gómez Garcia, Encarna B, Berger, Andreas, Bonanni, Bernardo, Hebon, Hansen, Thomas V O, Rhiem, Kerstin, Jønson, Lars, Wakeley, Katie, Garber, Judy, Foo, Claire, Toland, Amanda Ewart, Ejlertsen, Bent, Pedersen, Inge Sokilde, Ellis, Steve, van Os, Theo A M, Collée, J Margriet, van der Luijt, Rob B, Lubinski, Jan, Simard, Jacques, Izatt, Louise, Teixeira, Manuel R, Mariette, Frederique, Piedmonte, Marion, Volorio, Sara, Hoogerbrugge, Nicoline, Porteous, Mary, Mazoyer, Sylvie, Wang-Gohrke, Shan, Martínez-Bouzas, Cristina, Viel, Alessandra, Soucy, Penny, Side, Lucy, Olah, Edith, Jaworska-Bieniek, Katarzyna, Maugard, Christine, Vijai, Joseph, Beattie, Mary S, Godwin, Andrew K, Investigators, Kconfab, Geschwantler Kaulich, Daphne, Eeles, Ros, van der Kolk, Lizet, Adlard, Julian, Durda, Katarzyna, Steinemann, Doris, Nevanlinna, Heli, Douglas, Fiona, Lázaro, Conxi, Davidson, Rosemarie, Engel, Christoph, Robson, Mark, Preisler-Adams, Sabine, Healey, Sue, Zhang, Liying, Fink-Retter, Anneliese, Mulligan, Anna Marie, Terry, Mary B, Damiola, Francesca, Tea, Muy-Kheng, Friedman, Eitan, Tucker, Kathy, Couch, Fergus J, Glendon, Gord, Kast, Karin, Pfeiler, Georg, Bojesen, Anders, Sunde, Lone, Ramón Y Cajal, Teresa, Moreno, Leticia Thais, Aittomäki, Kristiina, Shimon, Shani Paluch, Loman, Niklas, Scuvera, Giulietta, de Lange, J L, Rebbeck, Timothy R, Konstantopoulou, Irene, Backes, Floor, Laitman, Yael, Andrés Conejero, Raquel, McGuffog, Lesley, Rodríguez, Gustavo, Radice, Paolo, Devilee, Peter, Chenevix-Trench, Georgia, Olopade, Olufunmilayo I, Daly, Mary B, Evans, Gareth, Menéndez, Mireia, Dorfling, Cecilia M, Meijers-Heijboer, Hanne E J, van der Hout, A H, Ehrencrona, Hans, Montagna, Marco, Phelan, Catherine M, Cook, Jackie, van Asperen, Christi J, Brewer, Carole, Tognazzo, Silvia, Arun, Banu K, Hopper, John, Gerdes, Anne-Marie, Kennedy, John, Guidugli, Lucia, Manoukian, Siranoush, Jakubowska, Anna, Antoniou, Antonis C, Cybulski, Cezary, Southey, Melissa, Singer, Christian F, Easton, Douglas F, Arnold, Norbert, Gronwald, Jacek, Niederacher, Dieter, Rappaport, Christine, van Rensburg, Elizabeth J, Herráez, Belén, Weitzel, Jeffrey N, Varesco, Liliana, Sinilnikova, Olga M, Greene, Mark H, Frost, Debra, Lindor, Noralane, Karlan, Beth Y, Slager, Susan, Infante, Mar, Kruse, Torben A, Domchek, Susan M, Barrowdale, Daniel, Steele, Linda, Szabo, Csilla I, Papi, Laura, Jensen, Uffe Birk, Peissel, Bernard, Tibiletti, Maria Grazia, Yannoukakos, Drakoulis, Cole, Trevor, Caldés, Trinidad, Offit, Kenneth, Fineberg, Elena, Walker, Lisa, Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. 2Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. 5Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain. 6IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. 7Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 8Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. 9Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain. 10Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Institut de Recerca (VHIR), and Universitat Autonoma de Barcelona, Barcelona, Spain. 11Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 12Molecular Diagnostics Laboratory IRRP, National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis, Athens, Greece. 13Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain. 14Medical Oncology Service, Hospital Clínico Lozano Blesa, San Juan Bosco, Zaragoza, Spain. 15Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada. 16Department of Oncology, Lund University, Lund, Sweden. 17Department of Oncology, Karolinska University Hospital, Stockholm, Sweden. 18Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 19Department of Oncology, Lund University Hospital, Lund, Sweden. 20Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. 21Center for Clinical Cancer Genet, Osorio, Ana, Milne, Roger L, Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco, Ignacio, de la Hoya, Miguel, Duran, Mercedes, Díez, Orland, Mai, Phuong L, Neuhausen, Susan L, Lejbkowicz, Flavio, Ottini, Laura, Lee, Andrew, Buys, Saundra S, Thomassen, Mads, Zaffaroni, Daniela, Andrulis, Irene, Benitez, Javier, Schmutzler, Rita Katharina, Eccles, Diana, Swe-Brca, Platte, Radka, Hodgson, Shirley, Tischkowitz, Marc, Meindl, Alfons, van Deurzen, Carolien H M, Nathanson, Katherine, Donaldson, Alan, Varon-Mateeva, Raymonda, Teulé, Alex, Walsh, Christine, Poppe, Bruce, Ditsch, Nina, Arver, Brita, Morrison, Patrick, Plendl, Hans Jörg, Sutter, Christian, Rantala, Johanna, Johannsson, Oskar Th, Janavicius, Ramunas, Wappenschmidt, Barbara, Stoppa-Lyonnet, Dominique, Brewster, Wendy, Olswold, Curtis, Ding, Yuan Chun, Rookus, Matti A, Lester, Jenny, John, Esther M, Gehrig, Andrea, Herzog, Josef, Lalloo, Fiona, Kauff, Noah, Whittemore, Alice S, Rau-Murthy, Rohini, Weeman, Kisa, Claes, Kathleen, Rutherford, Thomas, Gómez Garcia, Encarna B, Berger, Andreas, Bonanni, Bernardo, Hebon, Hansen, Thomas V O, Rhiem, Kerstin, Jønson, Lars, Wakeley, Katie, Garber, Judy, Foo, Claire, Toland, Amanda Ewart, Ejlertsen, Bent, Pedersen, Inge Sokilde, Ellis, Steve, van Os, Theo A M, Collée, J Margriet, van der Luijt, Rob B, Lubinski, Jan, Simard, Jacques, Izatt, Louise, Teixeira, Manuel R, Mariette, Frederique, Piedmonte, Marion, Volorio, Sara, Hoogerbrugge, Nicoline, Porteous, Mary, Mazoyer, Sylvie, Wang-Gohrke, Shan, Martínez-Bouzas, Cristina, Viel, Alessandra, Soucy, Penny, Side, Lucy, Olah, Edith, Jaworska-Bieniek, Katarzyna, Maugard, Christine, Vijai, Joseph, Beattie, Mary S, Godwin, Andrew K, Investigators, Kconfab, Geschwantler Kaulich, Daphne, Eeles, Ros, van der Kolk, Lizet, Adlard, Julian, Durda, Katarzyna, Steinemann, Doris, Nevanlinna, Heli, Douglas, Fiona, Lázaro, Conxi, Davidson, Rosemarie, Engel, Christoph, Robson, Mark, Preisler-Adams, Sabine, Healey, Sue, Zhang, Liying, Fink-Retter, Anneliese, Mulligan, Anna Marie, Terry, Mary B, Damiola, Francesca, Tea, Muy-Kheng, Friedman, Eitan, Tucker, Kathy, Couch, Fergus J, Glendon, Gord, Kast, Karin, Pfeiler, Georg, Bojesen, Anders, Sunde, Lone, Ramón Y Cajal, Teresa, Moreno, Leticia Thais, Aittomäki, Kristiina, Shimon, Shani Paluch, Loman, Niklas, Scuvera, Giulietta, de Lange, J L, Rebbeck, Timothy R, Konstantopoulou, Irene, Backes, Floor, Laitman, Yael, Andrés Conejero, Raquel, McGuffog, Lesley, Rodríguez, Gustavo, Radice, Paolo, Devilee, Peter, Chenevix-Trench, Georgia, Olopade, Olufunmilayo I, Daly, Mary B, Evans, Gareth, Menéndez, Mireia, Dorfling, Cecilia M, Meijers-Heijboer, Hanne E J, van der Hout, A H, Ehrencrona, Hans, Montagna, Marco, Phelan, Catherine M, Cook, Jackie, van Asperen, Christi J, Brewer, Carole, Tognazzo, Silvia, Arun, Banu K, Hopper, John, Gerdes, Anne-Marie, Kennedy, John, Guidugli, Lucia, Manoukian, Siranoush, Jakubowska, Anna, Antoniou, Antonis C, Cybulski, Cezary, Southey, Melissa, Singer, Christian F, Easton, Douglas F, Arnold, Norbert, Gronwald, Jacek, Niederacher, Dieter, Rappaport, Christine, van Rensburg, Elizabeth J, Herráez, Belén, Weitzel, Jeffrey N, Varesco, Liliana, Sinilnikova, Olga M, Greene, Mark H, Frost, Debra, Lindor, Noralane, Karlan, Beth Y, Slager, Susan, Infante, Mar, Kruse, Torben A, Domchek, Susan M, Barrowdale, Daniel, Steele, Linda, Szabo, Csilla I, Papi, Laura, Jensen, Uffe Birk, Peissel, Bernard, Tibiletti, Maria Grazia, Yannoukakos, Drakoulis, Cole, Trevor, Caldés, Trinidad, Offit, Kenneth, Fineberg, Elena, and Walker, Lisa
Abstract: To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access., Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

7. Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies

Author: Fulvio Ricceri, Joseph A. Rothwell, Amanda J. Cross, Graham G. Giles, Elisabete Weiderpass, Tilman Kühn, Emily Sonestedt, Yi Yang, Rudolf Kaaks, Valeria Pala, Anna Karakatsani, Dallas R. English, Rosario Tumino, Pilar Amiano, Antonia Trichopoulou, John L. Hopper, Leila Lujan-Barroso, Allison M. Hodge, Bengt Wallner, Ruth C. Travis, María Dolores López, Anne Tjønneland, Hazel M. Mitchell, Kostas Tsilidis, Domenico Palli, Harindra Jayasekara, Elio Riboli, Antonio Agudo, Robin Room, Heiner Boeing, Eva Ardanaz, Bas Bueno-de-Mesquita, Torkjel M. Sandanger, Pietro Ferrari, Robert J. MacInnis, Susana Merino, Andrew Haydon, Eleni Peppa, Marie-Christine Boutron-Ruault, Salvatore Panico, María José Sánchez, Marc J. Gunter, Hanna Sternby, Roger L. Milne, Gianluca Severi, Ana Lucia Mayen-Chacon, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), VicHealth Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT Medical Research Council, MRC: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1 British Heart Foundation, BHF Department of Health and Social Care, DH Cancer Research UK, CRUK: C570/ A16491, C8221/A19170, C864/A14136 World Cancer Research Fund, WCRF Food Standards Agency, FSA Stroke Association European Commission, EC National Health and Medical Research Council, NHMRC: 1074383, 209057, 396414, GNT1163120 Cancer Council Victoria Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Vetenskapsrådet, VR Consiglio Nazionale delle Ricerche, CNR Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Foundation for Alcohol Research and Education, FARE Hellenic Health Foundation, HHF, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414, GNT1163120, Cancer Council Victoria (Australia), Cancer Research UK, Grant/Award Numbers: C570/ A16491, C8221/A19170, C864/A14136, Catalan Institute of Oncology ‐ ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission (Directorate General for Health and Consumer Affairs), Foundation for Alcohol Research and Education (Australia), French Ministry of Health, Grant/Award Number: Grant GR‐IARC‐2003‐09‐12‐01, Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Santé et de la Recherche Médicale (France), Italian Association for Research on Cancer and the National Research Council (Italy), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, Medical Research Council (UK), Grant/Award Numbers: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1, Mutuelle Générale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK), Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), the Federal Ministry of Education and Research (Germany), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Institut Gustave Roussy Funding information, We thank Carine Biessy and Bertrand Hemon for their technical contribution to EPIC data used in this work. We are also grateful to all the EPIC participants who have been part of the project, and to the many members of the study teams who enabled this research. We thank the original MCCS investigators and the diligent team, who recruited the participants and who continue working on follow‐up, for their contribution. We also express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study, the Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ‐ ICO (Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). MCCS cohort recruitment was funded by Cancer Council Victoria ( https://www.cancervic.org.au/ ) and VicHealth ( https://www.vichealth.vic.gov.au/ ). The MCCS was further supported by Australian National Health and Medical Research Council (NHMRC) ( https://www.nhmrc.gov.au/ ) grants 209057, 396414 and 1074383, and ongoing follow‐up and data management has been funded by Cancer Council Victoria since 1995. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. Harindra Jayasekara is supported by NHMRC grant GNT1163120. John L. Hopper is a NHMRC Senior Principal Research Fellow. Yi Yang is supported by a Melbourne Research Scholarship from the University of Melbourne. Robin Room's position was funded by the Foundation for Alcohol Research and Education. The sponsors had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and and decision to submit the manuscript for publication.
Subjects: Male, Cancer Research, Gastroenterology, 0302 clinical medicine, Prospective Studies, Stomach cancer, Prospective cohort study, stomach cancer, biology, Stomach, Incidence, Hazard ratio, Smoking, cardia cancer, Cardia cancer, Middle Aged, Lifetime alcohol intake, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, medicine.anatomical_structure, Oncology, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, Consum d'alcohol, Female, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Helicobacter Infections, noncardia cancer, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Aged, Science & Technology, Helicobacter pylori, EPIC, lifetime alcohol intake, MCCS, business.industry, Càncer d'estómac, Kirurgi, Australia, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Noncardia cancer, medicine.disease, biology.organism_classification, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., National Health and Medical Research Council of Australia 1074383 209057 396414 GNT1163120, Canadian Institutes of Health Research (CIHR) Cancer Council Victoria, Cancer Research UK C570/A16491 C8221/A19170 C864/A14136, Catalan Institute of Oncology - ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission European Commission Joint Research Centre, Foundation for Alcohol Research and Education (Australia), French Ministry of Health GR-IARC-2003-09-12-01, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Junta de Andalucía, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Sante et de la Recherche Medicale (Inserm), Consiglio Nazionale delle Ricerche (CNR), Associazione Italiana per la Ricerca sul Cancro (AIRC), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC-UU_12015/1 MR/M012190/1 MR/N003284/, Mutuelle Generale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association (UK), British Heart Foundation, Department of Health (UK), Food Standards Agency (UK), Wellcome Trust, Swedish Cancer Society, Swedish Scientific Council (Sweden), Regional Government of Skane (Sweden), Federal Ministry of Education & Research (BMBF), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), Institut Gustave Roussy
Published: 2021

8. Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data

Author: Daniel F. Schmidt, Rory P. Wilson, Melanie Waldenberger, Laura Baglietto, Harindra Jayasekara, Benjamin Lehne, Graham G. Giles, Pierre Antoine Dugué, Jaspal S. Kooner, Melissa C. Southey, Xiaochuan Wang, Annette Peters, Karl-Heinz Ladwig, Dallas R. English, John C Chambers, Jihoon E. Joo, Christian Gieger, Roger L. Milne, Chol-Hee Jung, Gianluca Severi, Enes Makalic, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Melbourne School of Population and Global Health [Melbourne], University of Melbourne, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, W2 1PG, Melbourne Bioinformatics [Australia], The University of MelbourneParkville, VIC, Australia., Department of Clinical and Experimental Medicine, University of Pisa, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), München, Technische Universität München, German Research Center for Cardiovascular Disease (DZHK), Partner site Munich Heart Alliance, Institute of Epidemiology and Medical Biometry, University of Ulm, Munich, Germany, Ealing Hospital, Imperial College Healthcare NHS Trust, Monash University [Clayton], Nanyang Technological University [Singapour], Imperial College Healthcare NHS Trust Oregon Department of Agriculture, ODA: 16/136/68 279143 Wellcome Trust, WT: 084723/Z/08/Z, 090532, RP‐PG‐0407‐10371, 098381 Cancer Council Victoria: 1026892, 1027505, 251553, 209057, 1050198, 1011618, 1074383, 504711, 1043616 Bundesministerium für Bildung und Forschung, BMBF VicHealth British Heart Foundation, BHF: SP/04/002 Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München National Institute for Health Research, NIHR National Health and Medical Research Council, NHMRC: 1088405 Horizon 2020 Framework Programme, H2020: 643774 ERAB: The European Foundation for Alcohol Research, ERAB: ERAB 2018 – EA1817 Medical Research Council, MRC: G0601966, G0700931 National Medical Research Council, NMRC: NMRC/STaR/0028/2017, and This work (MCCS) was supported by the Australian National Health and Medical Research Council (NHMRC) (Grant 1088405). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC Grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases were ascertained through the Victorian Cancer Registry (VCR) and the Australian Cancer Database (Australian Institute of Health and Welfare). The nested case‐control methylation studies were supported by the NHMRC Grants 1011618, 1026892, 1027505, 1050198, 1043616, and 1074383. M.C.S. is an NHMRC Senior Research Fellow (1061177). The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research has been supported within the Munich Center of Health Sciences (MC‐Health), Ludwig‐Maximilians‐Universität, as part of LMUinnovativ. This work has received funding from the European Foundation for Alcohol Research (ERAB 2018 – EA1817). We thank all members of field staffs who were involved in the planning and conduct of the MONICA/KORA Augsburg studies. The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966, G0700931), the Wellcome Trust (084723/Z/08/Z, 090532, and 098381), the NIHR (RP‐PG‐0407‐10371), the NIHR Official Development Assistance (ODA, award 16/136/68), the European Union FP7 (EpiMigrant, 279143), and H2020 programs (iHealth‐T2D, 643774). We acknowledge support of the MRC‐PHE Centre for Environment and Health and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the Imperial College Healthcare NHS Trust, the NHS, the NIHR, or the Department of Health. We thank the participants and research staff who made the study possible. JC is supported by the Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research Investigator (STaR) Award (NMRC/STaR/0028/2017).
Subjects: Male, longitudinal data, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Physiology, Alcohol, Disease, Epigenesis, Genetic, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Prospective Studies, education.field_of_study, 0303 health sciences, DNA methylation, Confounding, Regression analysis, Methylation, Middle Aged, epigenome-wide association study, Substance abuse, Psychiatry and Mental health, 030220 oncology & carcinogenesis, Female, Alcohol consumption, Cohort study, Adult, Alcohol Drinking, Longitudinal data, alcohol consumption, Population, 03 medical and health sciences, Genetic, cross-sectional data, EWAS, HM450 assay, Aged, CpG Islands, Cross-Sectional Studies, Genome-Wide Association Study, Humans, DNA Methylation, Epigenetics, education, 030304 developmental biology, Pharmacology, business.industry, Alcohol Consumption, Cross-sectional Data, Dna Methylation, Epigenome-wide Association Study, Ewas, Hm450 Assay, Longitudinal Data, medicine.disease, 030227 psychiatry, chemistry, business, 030217 neurology & neurosurgery, Epigenesis
Abstract: Background:DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart.Methods:Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined using baseline peripheral blood samples from 5,606 adult Melbourne Collaborative Cohort Study (MCCS) participants. For a subset of 1,088 of them, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. Independent data from the LOLIPOP (N=4,042) and KORA (N=1,662) cohorts were used to replicate associations discovered in the MCCS.Results:Cross-sectional analyses identified 1,414 CpGs associated with alcohol intake at P-7, 1,243 of which had not been reported previously. Of these 1,243 novel associations, 1,078 were replicated (PConclusion:Our study indicates that, for middle-aged and older adults, alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with changes in alcohol consumption.
Published: 2021

9. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

Author: Michael O. Woods, Fränzel J.B. van Duijnhoven, Tilman Kühn, Graham G. Giles, Temitope O. Keku, Konstantinos K. Tsilidis, Andrew T. Chan, Mingyang Song, Michael Hoffmeister, Gad Rennert, Tabitha A. Harrison, Anna H. Wu, Kenneth Offit, Mark A. Jenkins, Elizabeth A Platz, Sabina Sieri, Noralane M Lindor, John D. Potter, D Timothy Bishop, Barbara L. Banbury, Anne M. May, Sonja I. Berndt, José María Huerta, Antonia Trichopoulou, Paul D.P. Pharoah, Niki Dimou, Christopher I. Li, Roger L. Milne, Marc J. Gunter, Hermann Brenner, Martha L. Slattery, Catherine M. Tangen, Gianluca Severi, Richard M. Martin, Nabila Kazmi, Ruth C. Travis, Sanford D. Markowitz, Jeroen R. Huyghe, Heather Hampel, Ulrike Peters, John L. Hopper, Brigid M. Lynch, Krasimira Aleksandrova, Alicja Wolk, Merete Ellingjord-Dale, Li Li, Bethany Van Guelpen, Sergi Castellví-Bel, Edward Giovannucci, Steven J Gallinger, Annika Lindblom, Cornelia M. Ulrich, Stephen B. Gruber, Stephanie L. Schmit, Jenny Chang-Claude, Lorena Moreno, Victor Moreno, Nikos Papadimitriou, Stephen N. Thibodeau, Elio Riboli, Sophia Harlid, Polly A. Newcomb, Pavel Vodicka, Demetrius Albanes, Bas Bueno-de-Mesquita, Maria J. Sánchez, Sarah J Lewis, Timothy Robinson, Daniel D Buchanan, Loic Le Marchand, Carlo La Vecchia, Robert E Schoen, Neil Murphy, Giovanna Masala, Evelyn M. Monninkhof, Jane C. Figueiredo, Andrea Gsur, Jochen Hampe, Vittorio Perduca, Li Hsu, Emily White, Peter T. Campbell, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, German Institute of Human Nutrition, Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Division of Cancer Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Harvard School of Public Health, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Ohio State University [Columbus] (OSU), FESTO, Universität Stuttgart [Stuttgart], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Genetics, HMNC Brain Health, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Mayo Clinic, Case Western Reserve University [Cleveland], Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Cancer Epidemiology Centre, Cancer Council Victoria, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, School of Public Health [London, UK] (Faculty of Medicine), Andalusian School of Public Health [Granada], Istituto Nazionale dei Tumori, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Mayo Clinic [Rochester], University of Oxford [Oxford], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], Nutrition and Metabolism Section, International Agency for Research on Cancer, [Papadimitriou,N, Dimou,N, Gunter,MJ, Murphy,N] Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Banbury,B, Harrison,TA, Hsu,L, Huyghe,JR, Li,CI, Newcomb,PA, Potter,JD, White,E, Peters,U] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Martin,RM, Kazmi,N] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [Martin,RM, Lewis,SJ, Robinson,TM] Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK. [Martin,RM] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. [Albanes,D, Berndt,SI] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA. [Aleksandrova,K] German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Bishop,DT] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. [Brenner,H, Hoffmeister,M] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Brenner,H] Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [Brenner,H] German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [Buchanan,DD, Giles,GG, Hopper,JL, Jenkins,MA, Lynch,B, Milne,R] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. [Buchanan,DD] Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Buchanan,DD] Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia [Bueno-de-Mesquita,B] Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, Netherlands. [Bueno-de-Mesquita,B] Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Bueno-de-Mesquita,B] ormer visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, London, UK. [Bueno-de-Mesquita,B] Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia. [Campbell,PT] Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. [Castellví-Bel,S, Moreno,L] Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [Chan,AT, Song,M] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chan,AT, Song,M] Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chang-Claude,J, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Chang-Claude,J] University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. [Figueiredo,JC] Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [Figueiredo,JC] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gallinger,SJ] Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Giles,GG, Milne,R] Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. [Giovannucci,E, Song,M] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. [Giovannucci,E, Song,M] Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. [Giovannucci,E] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Gruber,SB, Schmit,SL] Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gsur,A] Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. [Hampe,J] Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. [Hampel,H] Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. [Harlid,S] Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden. [Hopper,JL] Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. [Hsu,L] Department of Biostatistics, University of Washington, Seattle, WA, USA. [Huerta,JM, Moreno,V, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Keku,TO] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. [La Vecchia,C, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [La Vecchia,C] Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy. [Le Marchand,L] University of Hawaii Cancer Center, Honolulu, HI, USA. [Li,L] Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. [Lindblom,A] Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. [Lindblom,A] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Lindor,NM] Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. [Lynch,B] Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. [Markowitz,SD] Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [May,AM, Monninkhof,E] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA UTRECHT, Netherlands. [Milne,R] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Moreno,V] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Moreno,V] Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Newcomb,PA] School of Public Health, University of Washington, Seattle, WA, USA. [Offit,K] Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Offit,K] Department of Medicine, Weill Cornell Medical College, New York, NY, USA. [Perduca,V, Severi,G] CESP, Fac. de médecine - Univ. ParisSud, Fac. de médecine - UVSQ I, Université Paris-Saclay, Villejuif, France. [Perduca,V, Severi,G] Gustave Roussy, Villejuif, France. [Perduca,V] Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France. [Pharoah,PDP] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Platz,EA] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [Rennert,G] Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. [Rennert,G] 7Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. [Rennert,G] Clalit National Cancer Control Center, Haifa, Israel. [Sánchez,MJ] Andalusian School of Public Health, Biomedical Research Institute ibs.GRANADA, University of Granada, Granada, Spain. [Schmit,SL] Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Schoen,RE] Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Slattery,ML] Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. [Tangen,CM] SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Thibodeau,SN] Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Ulrich,CM] Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. [van Duijnhoven,FJB] Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. [Van Guelpen,B] Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. [Van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Vodicka,P] Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. [Vodicka,P] Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. [Vodicka,P] Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. [White,E, Peters,U] Department of Epidemiology, University of Washington, Seattle, WA, USA. [Wolk,A] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. [Woods,MO] Memorial University of Newfoundland, Discipline of Genetics, St. John’s, Canada. [Wu,AH] University of Southern California, Preventative Medicine, Los Angeles, CA, USA., This work was supported by the National Cancer Institute, the International Agency for Research on Cancer and a Cancer Research UK program grant (C18281/A19169 to RMM, SJL & NK). RMM was supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding sources for BCAC, CCFR, GECCO, and CORECT consortia are presented in detail in the appendix in the Supplementary material., Tsilidis, Konstantinos K [0000-0002-8452-8472], Martin, Richard M [0000-0002-7992-7719], Lewis, Sarah J [0000-0003-4311-6890], Robinson, Timothy M [0000-0003-0933-646X], Timothy Bishop, D [0000-0002-8752-8785], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Giles, Graham G [0000-0003-4946-9099], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hampel, Heather [0000-0001-7558-9794], Harlid, Sophia [0000-0001-8540-6891], Harrison, Tabitha A [0000-0002-4173-7530], María Huerta, José [0000-0002-9637-3869], Huyghe, Jeroen R [0000-0001-6027-9806], Jenkins, Mark A [0000-0002-8964-6160], La Vecchia, Carlo [0000-0003-1441-897X], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger [0000-0001-5764-7268], Moreno, Victor [0000-0002-2818-5487], Newcomb, Polly A [0000-0001-8786-0043], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul D P [0000-0001-8494-732X], Potter, John D [0000-0001-5439-1500], Rennert, Gad [0000-0002-8512-068X], Riboli, Elio [0000-0001-6795-6080], Schmit, Stephanie L [0000-0001-5931-1194], Schoen, Robert E [0000-0001-7153-2766], Van Guelpen, Bethany [0000-0002-9692-101X], Wolk, Alicja [0000-0001-7387-6845], Peters, Ulrike [0000-0001-5666-9318], Murphy, Neil [0000-0003-3347-8249], Apollo - University of Cambridge Repository, Tsilidis, Konstantinos K. [0000-0002-8452-8472], Martin, Richard M. [0000-0002-7992-7719], Lewis, Sarah J. [0000-0003-4311-6890], Timothy Bishop, D. [0000-0002-8752-8785], Buchanan, Daniel D. [0000-0003-2225-6675], Chan, Andrew T. [0000-0001-7284-6767], Giles, Graham G. [0000-0003-4946-9099], Harrison, Tabitha A. [0000-0002-4173-7530], Huyghe, Jeroen R. [0000-0001-6027-9806], Jenkins, Mark A. [0000-0002-8964-6160], Newcomb, Polly A. [0000-0001-8786-0043], Pharoah, Paul D. P. [0000-0001-8494-732X], Potter, John D. [0000-0001-5439-1500], Schmit, Stephanie L. [0000-0001-5931-1194], Schoen, Robert E. [0000-0001-7153-2766], and Pharoah, Paul DP [0000-0001-8494-732X]
Subjects: Oncology, Epidemiology, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Accelerometry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Mendelian Randomization Analysis [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Epidemiology of cancer, Accelerometry, Odds Ratio, lcsh:Science, skin and connective tissue diseases, Cancer genetics, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, Biobank, 3. Good health, 030220 oncology & carcinogenesis, ICEP, Factores de riesgo, medicine.medical_specialty, Science, 631/67/2324, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colorectal Neoplasms, Hereditary Nonpolyposis [Medical Subject Headings], Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], Humans, Epidemiologia, Exercise, VLAG, Cancer och onkologi, 45, 631/67/1347, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Colorectal Neoplasms/genetics, 030104 developmental biology, Analyses, Risk factors, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, lcsh:Q, Breast neoplasms, 0301 basic medicine, 631/67/1504/1885, Nutrition and Disease, General Physics and Astronomy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Factors, Neoplasias colorrectales, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Polymorphism, Single Nucleotide/genetics, Ejercicio físico, Neoplasias de la mama, Female, Colorectal Neoplasms, 631/67, 141, Breast Neoplasms, 45/23, Polymorphism, Single Nucleotide, Colorectal neoplasms, Càncer de mama, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Cancer epidemiology, 631/67/68, Internal medicine, Mendelian randomization, medicine, Journal Article, Life Science, Genetic Predisposition to Disease, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], business.industry, General Chemistry, Physical fitness, Confidence interval, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Condició física
Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI), International Agency for Research on Cancer, Cancer Research UK C18281/A19169, National Institute for Health Research (NIHR)
Published: 2020

10. Epigenetic Drift Association with Cancer Risk and Survival, and Modification by Sex

Author: Graham G. Giles, Daniel D. Buchanan, Melissa C. Southey, Allison M. Hodge, Gianluca Severi, Pierre Antoine Dugué, Dallas R. English, Chenglong Yu, Ee Ming Wong, Enes Makalic, John L. Hopper, Daniel F. Schmidt, Jihoon E. Joo, Monash University [Clayton], University of Melbourne, Victorian Comprehensive Cancer Centre [Melbourne, Australia] (V3C), Cancer Council Victoria [Melbourne, VIC, Australia], The Royal Melbourne Hospital, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Università degli Studi di Firenze = University of Florence (UniFI), VicHealth National Health and Medical Research Council, NHMRC: 1011618, 1026892, 1027505, 1043616, 1050198, 1074383, 1164455, 209057, 251553, 504711, GTN1155163 Cancer Council Victoria, Funding: MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. The nested case–control methylation studies were supported by the NHMRC grants 1011618, 1026892, 1027505, 1050198, 1043616 and 1074383. This work was further supported by NHMRC grant 1164455. M.C.S. is a recipient of a Senior Research Fellowship from the NHMRC (GTN1155163)., and HAL UVSQ, Équipe
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, [SDV]Life Sciences [q-bio], sex difference, cancer risk, Epigenetic drift, lcsh:RC254-282, Article, X chromosome, 03 medical and health sciences, 0302 clinical medicine, Prostate, Internal medicine, medicine, Epigenetics, Pre-diagnostic blood, cancer survival, DNA methylation, Proportional hazards model, business.industry, age-by-sex, Hazard ratio, Cancer, Methylation, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, ageing, 030220 oncology & carcinogenesis, business
Abstract: Simple Summary Ageing is the strongest cancer risk factor, and men and women exhibit different risk profiles in terms of incidence and survival. DNA methylation is known to strongly vary by age and sex. Epigenetic drift refers to age-related DNA methylation changes and the tendency for increasing discordance between epigenomes over time, but it remains unknown to what extent the epigenetic drift contributes to cancer risk and survival. The aims of this study were to identify age-associated, sex-associated and sexually dimorphic age-associated (age-by-sex-associated) DNA methylation markers and investigate whether age- and age-by-sex-associated markers are associated with cancer risk and survival. Our study, which used a total of 2754 matched case–control pairs with DNA methylation in pre-diagnostic blood, is the first large study to examine the association between sex-specific epigenetic drift and cancer development and progression. The results may be useful for cancer early diagnosis and prediction of prognosis. Abstract To investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case–control studies of colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869) and urothelial (n = 428) cancers, and mature B-cell lymphoma (n = 438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls)-replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios (HR)), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates for these CpGs using GS summary data were 94%, 86% and 91%, respectively. Significant associations for cancer risk and survival were identified at some individual age-related CpGs. Opposite to previous findings using epigenetic clocks, there was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Methylation at two CpGs overlapping TMEM49 and ARX genes was associated with survival of overall (HR = 0.91, p = 7.7 × 10−4) and colorectal (HR = 1.52, p = 1.8 × 10−4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.
Published: 2021

11. Tools for translational epigenetic studies involving formalin-fixed paraffin-embedded human tissue: applying the Infinium HumanMethyation450 Beadchip assay to large population-based studies

Author: Melissa C. Southey, Jihoon E. Joo, Dallas R. English, John L. Hopper, Graham G. Giles, Laura Baglietto, Liesel M. FitzGerald, Catriona McLean, Gianluca Severi, Roger L. Milne, Ee Ming Wong, Bodescot, Myriam, Department of Pathology, University of Melbourne, Department of Anatomical Pathology, The Alfred Hospital, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Epidemiology and Biostatistics, Cohort recruitment was funded by VicHealth and Cancer Council Victoria. This work was further supported by the National Health and Medical Research Council (NHMRC, and APP1011618 and APP1026892) and The Victorian Breast Cancer Research Consortium. MCS is a NHMRC SRF and VBCRC Group Leader. JLH is a NHMRC SPRF. LMF is the Cancer Council Victoria David Hill Fellow and is funded by a Movember and Cure Cancer Australia Foundation Young Investigator Grant awarded through Prostate Cancer Foundation of Australia’s Research Program.
Subjects: Genetics and Molecular Biology (all), Tissue Fixation, Breast tumour subtype, Bisulfite sequencing, Gene Expression, Triple Negative Breast Neoplasms, Bioinformatics, BRCA1, DNA methylation, Epigenetics, Formalin-fixed paraffin-embedded, HM450K beadchip, Population-based translational epigenetic studies, Adult, Aged, BRCA1 Protein, Cohort Studies, DNA Methylation, DNA, Neoplasm, Female, Fixatives, Formaldehyde, Humans, Middle Aged, Oligonucleotide Array Sequence Analysis, Paraffin Embedding, Epigenesis, Genetic, Genome, Human, Biochemistry, Genetics and Molecular Biology (all), Medicine (all), Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Technical Note, Medicine(all), 0303 health sciences, education.field_of_study, Genome, General Medicine, Methylation, 3. Good health, 030220 oncology & carcinogenesis, Human, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetic, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, 030304 developmental biology, Biochemistry, Genetics and Molecular Biology(all), DNA, medicine.disease, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Neoplasm, Human genome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Epigenesis
Abstract: Background Large population-based translational epigenetic studies are emerging due to recent technological advances that have made molecular analyses possible. For example, the Infinium HumanMethylation450 Beadchip (HM450K) has enabled studies of genome-wide methylation on a scale not previously possible. However, application of the HM450K to DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour material has been more challenging than application to high quality DNA extracted from blood. To facilitate the application of this assay consistently across a large number of FFPE tumour-enriched DNA samples we have devised a modification to the HM450K protocol for FFPE that includes an additional quality control (QC) checkpoint. Results QC checkpoint 3 was designed to assess the presence of DNA after bisulfite conversion and restoration, just prior to application of the HM450K assay. DNA was extracted from 474 archival FFPE breast tumour material. Five samples did not have a detectable amount of DNA with an additional 42 failing to progress past QC checkpoint 3. Genome-wide methylation was measured for the remaining 428 tumour-enriched DNA. Of these, only 4 samples failed our stringent HM450K data criteria thus representing a 99 % success rate. Using prior knowledge about methylation marks associated with breast cancer we further explored the quality of the data. Twenty probes in the BRCA1 promoter region showed increased methylation in triple-negative breast cancers compared to Luminal A, Luminal B and HER2-positive breast cancer subtypes. Validation of this observation in published data from The Cancer Genome Atlas (TCGA) Network (obtained from DNA extracted from fresh frozen tumour samples) confirms the quality of the data obtained from the improved protocol. Conclusions The modified protocol is suitable for the analysis of FFPE tumour-enriched DNA and can be systematically applied to hundreds of samples. This protocol will have utility in population-based translational epigenetic studies and is applicable to a wide variety of translated studies interested in analysis of methylation and its role in the predisposition to disease and disease progression. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1487-z) contains supplementary material, which is available to authorized users.
Published: 2015

12. Acoustic neuroma risk in relation to mobile telephone use: results of the INTERPHONE international case-control study

Author: L. Montestruq, Gabriele Berg-Beckhoff, Anthony J. Swerdlow, N Yamaguchi, Maria Blettner, Joachim Schüz, Neil Pearce, Louise Nadon, Anna Lahkola, C. Johansen, Daniel Krewski, Bruce K. Armstrong, Anne-Sophie Evrard, Tore Tynes, Monika Moissonnier, J Siemiatycki, Ivano Iavarone, Anders Ahlbom, Avital Jarus-Hakak, Martine Vrijheid, M. Bernard, K. G. Blaasaas, Alistair Woodward, S. J. Hepworth, Salminen T, Isabelle Deltour, J Brown, Elisabeth Cardis, Martine Hours, Angela Chetrit, Päivi Kurttio, Patricia A. McKinney, Sigrid Lönn, Maria Feychting, Lars Klaeboe, Siegal Sadetzki, Brigitte Schlehofer, Helle Collatz Christensen, Toru Takebayashi, Interphone Study Grp, Susanna Lagorio, Anssi Auvinen, G.G. Giles, Angus Cook, M. M McBride, Minouk J. Schoemaker, Marie-Élise Parent, Kenneth Muir, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), International Agency for Cancer Research (IACR), IMIM-Hospital del Mar, Generalitat de Catalunya, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Sydney Cancer Centre and School of Public Health, The University of Sydney, Cancer Epidemiology Centre, The Cancer Council Victoria, School of Public Health and Hospital Research Center, Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], Cancer Research Centre, BC Cancer Agency (BCCRC), Danish Cancer Society, Institute of Cancer Epidemiology, Radiation and Nuclear Safety Authority [Helsinki] (STUK), Département Transport, Santé, Sécurité (IFSTTAR/TS2), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Lyon, Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg - Universität Mainz (JGU), Department of Epidemiology and International Public Health, Universität Bielefeld = Bielefeld University-Faculty of Public Health, Unit of Environmental Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, National Centre for Epidemiology Surveillance and Health Promotion, National Institute of Health, Department of Preventive Medicine and Public Health, University School of Medicine, Department of Public Health, University of Otago [Dunedin, Nouvelle-Zélande], Norwegian Radiation Protection Authority, The Cancer Registry of Norway, Norwegian Armed Forces Medical Services, The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], University of Leeds, The Health Science Research Institute, University of Warwick [Coventry], Institute of Cancer Research, Institute of cancer research, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, This work was supported by funding from the European Fifth Framework Program, ‘Quality of Life and Management of Living Resources’ (contract QLK4-CT-1999901563) and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers’ Forum and GSM Association. Provision of funds to the INTERPHONE study investigators via the UICC was governed by agreements that guaranteed INTERPHONE's complete scientific independence. The terms of these agreements are publicly available at http://www.iarc.fr/en/research-groups/RAD/RCAd.html.The Australian centre was supported by the Australian National Health and Medical Research Council (EME Grant 219129) with funds originally derived from mobile phone service licence fees, Julianne Brown was partly supported by an Australian Postgraduate Award. Cancer Council NSW and Cancer Council Victoria provided most of the infrastructure for the project in Australia.The Canadian centres in Ottawa/Vancouver were supported by a university–industry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR university–industry partnerships program also includes provisions that ensure complete scientific independence of the investigators. D. Krewski is the Natural Sciences and Engineering Research Council of Canada Chair in Risk Science at the University of Ottawa.The Canada – Montreal study was primarily funded by a grant from the Canadian Institutes of Health Research (project 15 MOP-42525). Additionally, Dr Siemiatycki's research team was partly funded by the Canada Research Chair programme and by the Guzzo-CRS Chair in Environment and Cancer. Dr Parent had a salary award from the Fonds de la recherche en santé du Québec.Additional funding for the study in France was provided by l’Association pour la Recherche sur le Cancer (ARC) [Contrat No. 5142] and three network operators (Orange, SFR, Bouygues Télécom). The funds provided by the operators represented 5% of the total cost of the French study and were governed by contracts guaranteeing the complete scientific independence of the investigators.The Finnish Interphone study received additional national funding from Emil Aaltonen Foundation and Academy of Finland (Grant No. 80921).The German Interphone study received additional national funding from the 'Deutsches Mobilfunkforschungsprogramm [German Mobile Phone Research Program]' of the German Federal Ministry of Environment, Nuclear Safety, and Nature Protection, the Ministry of Environment and Traffic of the state of Baden-Württemberg, the Ministry of Environment of the state of North Rhine-Westphalia, and the MAIFOR Programme of the University of Mainz.The Japanese Interphone study was fully funded by the Ministry of Internal Affairs and Communications of Japan.Funding in New Zealand for this project was provided by the Health Research Council of New Zealand, the Cancer Society of New Zealand, the Wellington Medical Research Foundation, the Hawke's Bay Medical Research Foundation and the Waikato Medical Research Foundation.The Swedish centre was additionally supported by the Swedish Research Council and the Swedish Cancer Society.The UK North study received additional funding from the Health and Safety Executive, the Department of Health, the Mobile Telecommunications, Health and Research (MTHR) program, and the Scottish Executive. The University of Leeds received some financial support on behalf of the 4 centres of the ‘UK North Study’ from the UK Network Operators (O2, Orange, T-Mobile, Vodafone, ‘3’) under legal signed contractual agreements which guaranteed complete independence for the scientific investigators.The Southeast England Centre wishes to acknowledge additional funding from the Mobile Telecommunications, Health and Research (MTHR) programme. The views expressed in this publication are those of the authors and not necessarily of the funders., and The INTERPHONE Study Group
Subjects: Male, Cancer Research, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, Epidemiology, MESH: Electromagnetic Fields, Decile, MESH: Glioma, 0302 clinical medicine, Risk Factors, Phone, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Meningeal Neoplasms, Odds Ratio, Medicine, Mobile phones, MESH: Middle Aged, Brain Neoplasms, Brain tumour, Glioma, Neuroma, Acoustic, MESH: Follow-Up Studies, Middle Aged, Prognosis, MESH: Case-Control Studies, 3. Good health, Survival Rate, Oncology, Reporting bias, 030220 oncology & carcinogenesis, Censoring (clinical trials), MESH: Brain Neoplasms, Female, Adult, MESH: Survival Rate, Acoustic neuroma, Radiofrequency electromagnetic fields, MESH: Prognosis, MESH: International Agencies, 03 medical and health sciences, Electromagnetic Fields, Vestibular schwannoma, Humans, MESH: Humans, business.industry, International Agencies, MESH: Adult, Odds ratio, medicine.disease, MESH: Meningeal Neoplasms, Confidence interval, MESH: Male, MESH: Odds Ratio, MESH: Cellular Phone, Mobile phone, Case-Control Studies, business, MESH: Female, Cell Phone, 030217 neurology & neurosurgery, Follow-Up Studies, Demography, MESH: Neuroma, Acoustic
Abstract: Background: The rapid increase in mobile telephone use has generated concern about possible health risks of radiofrequency electromagnetic fields from these devices. Methods: A case-control study of 1105 patients with newly diagnosed acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13 countries using a common protocol. Past mobile phone use was assessed by personal interview. In the primary analysis, exposure time was censored at one year before the reference date (date of diagnosis for cases and date of diagnosis of the matched case for controls); analyses censoring exposure at five years before the reference date were also done to allow for a possible longer latent period. Results: The odds ratio (OR) of acoustic neuroma with ever having been a regular mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for >= 10 years after first regular mobile phone use was 0.76 (0.52-1.11). There was no trend of increasing ORs with increasing cumulative call time or cumulative number of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of cumulative call time. In the 10th decile (>= 1640 h) of cumulative call time, the OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use in those with >= 1640 h of accumulated mobile phone use. With censoring at 5 years before the reference date the OR for >= 10 years after first regular mobile phone use was 0.83 (0.58-1.19) and for >= 1640 h of cumulative call time it was 2.79(1.51-5.16). but again with no trend in the lower nine deciles and with the lowest OR in the 9th decile. In general, ORs were not greater in subjects who reported usual phone use on the same side of the head as their tumour than in those who reported it on the opposite side, but it was greater in those in the 10th decile of cumulative hours of use. Conclusions: There was no increase in risk of acoustic neuroma with ever regular use of a mobile phone or for users who began regular use 10 years or more before the reference date. Elevated odds ratios observed at the highest level of cumulative call time could be due to chance, reporting bias or a causal effect. As acoustic neuroma is usually a slowly growing tumour, the interval between introduction of mobile phones and occurrence of the tumour might have been too short to observe an effect, if there is one. (C) 2011 Elsevier Ltd. All rights reserved.
Published: 2011

13. Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries

Author: Lynne D. Richardson, Elisabeth Cardis, Martine Vrijheid, Alistair Woodward, Graham G. Giles, Rodrigo Villegas, Jordi Figuerola, Marie-Élise Parent, Daniel Krewski, Bruce K. Armstrong, Martine Hours, Julianne Brown, Avital Jarus-Hakak, L. Montestruq, Louise Nadon, Angela Chetrit, Chen Hoffmann, Siegal Sadetzki, Mary L. McBride, Joseph D. Bowman, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Sydney School of Public Health, The University of Sydney, Engineering and Physical Hazards Branch, National Institute for Occupational Safety and Health, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for MEGA Epidemiology, University of Melbourne-School of Population Health, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), McLaughlin Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], BC Cancer Research Centre, BC Cancer Agency (BCCRC), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Cancer and Radiation Epidemiology Unit, Chaim Sheba Medical Center-Gertner Institute, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], School of Population Health, University of Auckland [Auckland], Department of Diagnostic Imaging, Chaim Sheba Medical Center, Department of Population health, Hospital Research Centre-University of Montreal, Funding for the Interphone Study was provided by the European Fifth Framework Program, 'Quality of Life and Management of Living Resources' (contract QLK4-CT-1999901563), the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers' Forum and GSM Association. Provision of funds to the Interphone Study investigators via the UICC was governed by agreements that guaranteed Interphone's complete scientific independence. The terms of these agreements are publicly available at http://www.iarc.fr/en/research-groups/RAD/RCAd.html Specific additional funds were provided for the development and analysis of the radio frequency exposure gradient and by the Fondation Santé et Radiofréquences, France and the Bundesamt fuer Strahlenschutz, Germany. The Australian centre was supported by the National Health and Medical Research Council (EME grant 219129), and BKA was supported by the University of Sydney Medical Foundation Program Grant and Julianne Brown by an Australian Postgraduate Award. The Cancer Council NSW and the Cancer Council Victoria provided most of the infrastructure for the project in Australia. The Canada-Montréal data collection was funded by a grant from the Canadian Institutes of Health Research (project MOP-42525). Additionally, Dr Siemiatycki's research team was partly funded by the Canada Research Chair programme and by the Guzzo-CRS Chair in Environment and Cancer. Dr. Parent had salary support from the Fonds de recherche en santé du Québec. The other Canadian centres were supported by a universityeindustry partnership grant from the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association. The CIHR universityeindustry partnerships program also includes provisions that ensure complete scientific independence of the investigators. DK is the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa. Additional funding for the study in France was provided by l'Association pour la Recherche sur le Cancer (ARC) (contract 5142) and three network operators (Orange, SFR, Bouygues Télécom). The funds provided by the operators represented 5% of the total cost of the French study and were governed by contracts guaranteeing the complete scientific independence of the investigators. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation and the Cancer Society of New Zealand. The findings and conclusions in this paper have not been formally disseminated by the National Institute for Occupational Safety and Health and should not be construed to represent any agency determination or policy.
Subjects: Oncology, Male, epidemiological study, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, Radio Waves, non-ionising radiation, MESH: Logistic Models, MESH: Meningioma, MESH: Radio Waves, MESH: Electromagnetic Fields, MESH: Glioma, 0302 clinical medicine, MESH: New Zealand, MESH: Risk Factors, Mobile phones, 030212 general & internal medicine, MESH: Middle Aged, ionising radiation, Brain Neoplasms, MESH: Israel, risk assessment, Brain, MESH: Case-Control Studies, RF exposure assessment, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Original Article, epidemiology, Female, physics, Algorithms, electromagnetic fields, medicine.medical_specialty, MESH: Radiation Dosage, Rf exposure, MESH: Australia, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiation Dosage, Meningioma, 03 medical and health sciences, MESH: Canada, Glioma, Internal medicine, medicine, cancer, Humans, MESH: Humans, business.industry, MESH: Time Factors, Public Health, Environmental and Occupational Health, Case-control study, MESH: Adult, Odds ratio, medicine.disease, MESH: Meningeal Neoplasms, hygiene/occupational hygiene, MESH: Male, MESH: Odds Ratio, Surgery, nervous system diseases, MESH: France, Increased risk, Multicenter study, MESH: Cellular Phone, business, MESH: Female, Cell Phone
Abstract: International audience; OBJECTIVES: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. METHODS: Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. RESULTS: ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. CONCLUSIONS: There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.
Published: 2011

14. The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density

Author: Sarah V. Ward, Anya Burton, Rulla M. Tamimi, Ana Pereira, Maria Luisa Garmendia, Marina Pollan, Norman Boyd, Isabel dos-Santos-Silva, Gertraud Maskarinec, Beatriz Perez-Gomez, Celine Vachon, Hui Miao, Martín Lajous, Ruy López-Ridaura, Kimberly Bertrand, Ava Kwong, Giske Ursin, Eunjung Lee, Huiyan Ma, Sarah Vinnicombe, Sue Moss, Steve Allen, Rose Ndumia, Sudhir Vinayak, Soo-Hwang Teo, Shivaani Mariapun, Beata Peplonska, Agnieszka Bukowska-Damska, Chisato Nagata, John Hopper, Graham Giles, Vahit Ozmen, Mustafa Erkin Aribal, Joachim Schüz, Carla H. Van Gils, Johanna O. P. Wanders, Reza Sirous, Mehri Sirous, John Hipwell, Jisun Kim, Jong Won Lee, Caroline Dickens, Mikael Hartman, Kee-Seng Chia, Christopher Scott, Anna M. Chiarelli, Linda Linton, Anath Arzee Flugelman, Dorria Salem, Rasha Kamal, Valerie McCormack, Jennifer Stone, NIH - National Cancer Institute (NCI) (Estados Unidos), International Agency for Research on Cancer, Cancer Council Western Australia (Australia), University of Western Australia (Australia), Australia VicHealth, Cancer Council Victoria (Australia), National Health and Medical Research Council (Australia), National Breast Cancer Foundation (Australia), National Cancer Institute (Canada), Fondecyt (Chile), World Cancer Research Fund International, Larry Ellison Foundation, Isfahan University of Technology (Irán), Israel Cancer Association, Asan Medical Center (Korea), Malaysia Sime Darby LPGA Tournament, Ministry of Education University (Malasia), University of Malaya (Malasia), Consejo Nacional de Ciencia y Tecnología (México), American Institute for Cancer Research, Unión Europea. Comisión Europea, Ministry of Health (Holanda), Dutch Cancer Society (Holanda), Netherlands Organisation for Health Research and Development, National Medical Research Council (Singapur), National University Cancer Institute (Singapur), South Africa Pink Drive, Instituto de Salud Carlos III, Federación Española de Padres de Niños con Cáncer, Turkey-Roche Mustahzarlari San, Engineering and Physical Sciences Research Council (Reino Unido), Breast Cancer Campaign (Reino Unido), Cancer Research UK (Reino Unido), Da Costa Foundation, and Susan G. Komen Breast Cancer Foundation
Subjects: Adult, Breast Neoplasms/diagnostic imaging, Menarche, Height, Mammography/methods, Breast Neoplasms, Breast cancer, Cross-Sectional Studies, Population Groups, Pregnancy, Risk Factors, Humans, Female, Mammographic density, Mammography, Breast Density
Abstract: Background: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. Methods: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. Results: In pooled analyses, later age at menarche was associated with higher per cent density (β√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (β√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (β√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (β√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. Conclusions: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density. This work was supported by the US National Cancer Institute at the National Institutes of Health [R03CA167771]; the International Agency for Research on Cancer; the University of Western Australia [Research Collaboration Award] and the Cancer Council Western Australia [Capacity Building and Collaboration Grant]. Original studies were supported, according to country by: Australia VicHealth; Cancer Council Victoria; Australian National Health and Medical Research Council [209057, 251,553 and 504711]; Australian National Breast Cancer Foundation [to JSt]; Canada the National Cancer Institute of Canada [to NFB]; Chile Fondecyt [11100238 to MLG, 1120326, 1130277, 3130532]; World Cancer Research Fund [2010/245]; Ellison Medical Foundation Grant [to AP]; Iran Isfahan University of Medical Sciences; Israel The Israel Cancer Association; Republic of Korea Asan Medical Center [2010-0811]; Malaysia Sime Darby LPGA Tournament; Ministry of Education University Malaya [High Impact Research Grant UM.C/HIR/MOHE/06]; University Malaya [Research Grant UMRG RP046B-15HTM]; Mexico National Council of Science and Technology (Mexico); the American Institute for Cancer Research [10A035]; Netherlands EPIC-NL-Europe against Cancer Programme of the European Commission (SANCO); Dutch Ministry of Health; Dutch Cancer Society; ZonMW the Netherlands Organisation for Health Research and Development; World Cancer Research Fund (WCRF); Poland Polish-Norwegian Research Programme [PNRF-243-AI-1/07]; Singapore National Medical Research Council [Clinician Scientist Award]; National University Cancer Institute Singapore (NCIS) Centre grant programme from National Medical Research Council; South Africa Pink Drive; Spain Spain’s Health Research Fund (Fondo de Investigacion Santiaria) [PI060386 and PS09/0790]; Spanish Federation of Breast Cancer Patients (FECMA) [EPY1169-10]; Turkey-Roche Mustahzarlari San. A.S., Istanbul, Turkey; UK UK Engineering and Physical Sciences Research Council [EP/K020439/1 to JHi]; Breast Cancer Campaign [2007MayPR23], Cancer Research UK [G186/11 and C405/A14565]; Da Costa Foundation UK; USA National Cancer Institute [R01CA85265, R37 CA54281, R01 CA97396, P50 CA116201, R01 CA177150 and R01 CA140286]; Cancer Center Support Grant [CA15083; CA131332, CA124865, UM1 CA186107 and UM1 CA176726]; the Susan G. Komen Foundation. Sí
Published: 2022

15. Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

Author: Chen, Hongjie, Fan, Shaoqi, Stone, Jennifer, Thompson, Deborah J, Douglas, Julie, Li, Shuai, Scott, Christopher, Bolla, Manjeet K, Wang, Qin, Dennis, Joseph, Michailidou, Kyriaki, Li, Christopher, Peters, Ulrike, Hopper, John L, Southey, Melissa C, Nguyen-Dumont, Tu, Nguyen, Tuong L, Fasching, Peter A, Behrens, Annika, Cadby, Gemma, Murphy, Rachel A, Aronson, Kristan, Howell, Anthony, Astley, Susan, Couch, Fergus, Olson, Janet, Milne, Roger L, Giles, Graham G, Haiman, Christopher A, Maskarinec, Gertraud, Winham, Stacey, John, Esther M, Kurian, Allison, Eliassen, Heather, Andrulis, Irene, Evans, D Gareth, Newman, William G, Hall, Per, Czene, Kamila, Swerdlow, Anthony, Jones, Michael, Pollan, Marina, Fernandez-Navarro, Pablo, McConnell, Daniel S, Kristensen, Vessela N, NBCS Investigators, Rothstein, Joseph H, Wang, Pei, Habel, Laurel A, Sieh, Weiva, Dunning, Alison M, Pharoah, Paul, Easton, Douglas F, Gierach, Gretchen L, Tamimi, Rulla M, Vachon, Celine M, Lindström, Sara, Unión Europea. Comisión Europea. H2020, Canadian Institutes of Health Research, Quebec Breast Cancer Foundation, Government of Quebec (Canadá), National Institutes of Health (Estados Unidos), Unión Europea. Comisión Europea. 7 Programa Marco, Cancer Research UK (Reino Unido), Susan G. Komen Breast Cancer Foundation, Ovarian Cancer Research Foundation (Astrualia), Australian Breast Cancer Family Study, NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), New South Wales Cancer Council (Reino Unido), Victorian Health Promotion Foundation, Victorian Cancer Agency, National Breast Cancer Foundation (Australia), Cancer Australia, Universitätsklinikum Erlangen (Alemania), Cancer Council Western Australia (Australia), Consorcio Gallego de Cáncer de Mama (BREOGAN), Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Galicia Sur Biomedical Foundation, Xunta de Galicia (España), Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Ministerio de Economía y Competitividad (España), Canadian Cancer Society, NIHR - Manchester Biomedical Research Center, Cancer Council Queensland (Australia), Cancer Council New South Wales (Australia), Cancer Council Victoria (Australia), Cancer Council Tasmania (Australia), Cancer Council South (Australia), United States Army Medical Research and Development Command, NIH - NCI-Specialized Programs of Research Excellence (SPORE) in Breast Cancer (Estados Unidos), The Research Council of Norway (Noruega), Southern and Eastern Norway Regional Health Authority (Noruega), Norwegian Cancer Society, Agency for Science, Technology and Research (Singapur), Institute of Cancer Research (Reino Unido), NIHR - Biomedical Research Centre (Reino Unido), Dennis, Joseph [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Lindström, Sara [0000-0002-7137-7281], and Apollo - University of Cambridge Repository
Subjects: Genome-wide association study (GWAS), Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Breast Neoplasms, Polymorphism, Single Nucleotide, Breast cancer, Phenotype, Humans, Female, Genetic Predisposition to Disease, ddc:610, Transcriptome, Mammographic density, Research Article, Transcriptome-wide association study (TWAS), Breast Density, Genome-Wide Association Study
Abstract: Background: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. Methods: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. Results: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p
Published: 2022
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16. Discovery of common and rare genetic risk variants for colorectal cancer

Author: Charles M. Connolly, Deborah A. Nickerson, Jian Gong, Sébastien Küry, Barbara Pardini, Brent W. Zanke, Andrea Gsur, Jochen Hampe, Coral Arnau-Collell, M. Henar Alonso, Elio Riboli, Annika Lindblom, Ulrike Peters, Gad Rennert, Tabitha A. Harrison, Lori C. Sakoda, Caroline McNeil, Flavio Lejbkowicz, Hyun Min Kang, David J. Hunter, Martha L. Slattery, Miguel Rodríguez-Barranco, Christina Bamia, Satu Männistö, Timothy J. Key, W. James Gauderman, Gonçalo R. Abecasis, Sanford D. Markowitz, Laurence N. Kolonel, Mark A. Jenkins, Yi Lin, Robin Myte, Hedy S. Rennert, Neil Murphy, Antonia Trichopoulou, Christopher I. Li, Ross L. Prentice, Sai Chen, Stephanie J. Weinstein, Kristin E. Anderson, Hua Ling, Mitul Shah, Philipp Hofer, Wen Yi Huang, Sergi Castellví-Bel, Susanna C. Larsson, Maria Dolores Chirlaque, Wei Zheng, Stephanie L. Schmit, Cecelia A. Laurie, Soo-Chin Lee, David Forman, Andrea N. Burnett-Hartman, Giovanna Masala, Sarah C. Nelson, Michael O. Woods, Charles Kooperberg, Qing Zhang, Sonja I. Berndt, Christopher S. Carlson, Katja Butterbach, Hyeong Rok Kim, Rebecca D. Jackson, David Van Den Berg, Michael C. Bassik, Amanda J. Cross, Sushma S. Thomas, Clemens Schafmayer, Anna H. Wu, Douglas F. Easton, Robert W. Haile, Ludmila Vodickova, Graham G. Giles, Yu Ru Su, Jenny Chang-Claude, Lorena Moreno, Peter C. Scacheri, Stefanie Brezina, Min-Ho Shin, Steven Gallinger, Bethany Van Guelpen, Daniel D. Buchanan, Roger L. Milne, Stephen J. Chanock, Tin Louie, Tameka Shelford, Emily White, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Roxann G. Ingersoll, Temitope O. Keku, Stephanie A. Bien, Fredrick R. Schumacher, Wan-Ling Hsu, Amanda E. Toland, John S. Grove, Noralane M. Lindor, Faye Elliott, Leon Raskin, Heather Hampel, Joshua D. Smith, Vicente Martín, David V. Conti, Sjoerd G. Elias, Henk J. van Kranen, Manish Gala, Daniela Seminara, Syed H.E. Zaidi, Suzanne M. Leal, Tilman Kühn, Korbinian Weigl, Marc J. Gunter, Cornelia M. Ulrich, Peyton Greenside, Victor Moreno, John D. Potter, Michael Hoffmeister, Eric J. Jacobs, Catherine M. Tangen, Jihyoun Jeon, Fränzel J.B. Van Duijnhoven, Andrew T. Chan, Stephen B. Gruber, John A. Baron, Alicja Wolk, Edith J. M. Feskens, Demetrius Albanes, Amit Joshi, Bette J. Caan, Polly A. Newcomb, Stéphane Bézieau, Elizabeth M. Gillanders, Anshul Kundaje, Elizabeth A. Platz, Michael Wainberg, Sun-Seog Kweon, C. Roland Wolf, Gemma Ibáñez-Sanz, Shuji Ogino, Emiko Kobayashi, Richard B. Hayes, Patrick S. Parfrey, Katarina Cuk, Stephen N. Thibodeau, Kenneth Offit, David Duggan, Sophia Harlid, Pavel Vodicka, Juergen Boehm, Christa Stegmaier, Jeroen R. Huyghe, Joseph Vijai, Sang-Hee Cho, Elizabeth W. Pugh, Rachel Pearlman, Alessio Naccarati, Marilena Melas, Graham Casey, Jane Romm, Stephan Buch, Phyllis J. Goodman, Albert de la Chapelle, John L. Hopper, Zsofia K. Stadler, Corinne E. Joshu, Liesel M. FitzGerald, Wolfgang Lieb, Aung Ko Win, Keith R. Curtis, Hermann Brenner, Christopher K. Edlund, Li Hsu, Conghui Qu, Peter T. Campbell, Robert E. Schoen, Heiner Boeing, D. Timothy Bishop, Kimberly F. Doheny, Sabina Sieri, Barbara L. Banbury, Mathieu Lemire, Jane C. Figueiredo, Gregory Idos, Katerina Shulman, Thomas J. Hudson, Melissa C. Southey, Duncan C. Thomas, Paul D.P. Pharoah, Mila Pinchev, Vittorio Perduca, Rocky Fischer, Volker Arndt, William M. Grady, Nasa Sinnott-Armstrong, N. Charlotte Onland-Moret, David M. Levine, Li Li, Dallas R. English, Health Research Board - Ireland, Department of Medical Genetics, HMNC Brain Health, Case Western Reserve University [Cleveland], National Cancer Institute, NIH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Division of Cancer Epidemiology, Cancer Genome Project, The Wellcome Trust Sanger Institute [Cambridge], Division of Signaling Biology, Ontario Cancer Institute, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), National Institute of Standards and Technology [Gaithersburg] (NIST), Ohio State University [Columbus] (OSU), Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Epidemiology Centre, Cancer Council Victoria, Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Northern and Yorkshire Cancer Registry and Information Service, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, London School of Hygiene and Tropical Medicine (LSHTM), Fraunhofer Institute for Manufacturing Engineering and Automation (Fraunhofer IPA), Fraunhofer (Fraunhofer-Gesellschaft), Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Department of Mathematics, University of Warwick, Warwick Mathematics Institute (WMI), University of Warwick [Coventry]-University of Warwick [Coventry], Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Tata Memorial Centre, Cancer Epidemiology Unit, University of Oxford [Oxford], Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, National University Health System, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Dell-EMC, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], University Medical Center [Utrecht], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, Department of Epidemiology and Biostatistics, Imperial College London, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Department of Laboratory Medicine and Department of Pathology, Mayo Clinic College of Medicine, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Dundee Technopole, CXR Biosciences Ltd, Karolinska Institutet [Stockholm], CINTRA / SEEE Nanyang Technological University, Nanyang Technological University [Singapour], Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Department of Preventive Medicine, University of Southern California (USC), Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Medstar Research Institute, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Wageningen University and Research Centre [Wageningen] (WUR), Mount Sinai Hospital (MSH), Fraunhofer Institute for Manufacturing Engineering and Automation [Stuttgart] (IPA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Czech Academy of Sciences [Prague] (ASCR), Huyghe, Jeroen R [0000-0001-6027-9806], Harrison, Tabitha A [0000-0002-4173-7530], Chen, Sai [0000-0003-3106-5643], Schmit, Stephanie L [0000-0001-5931-1194], Jeon, Jihyoun [0000-0001-7003-3412], Schumacher, Fredrick R [0000-0002-3073-7463], Nelson, Sarah C [0000-0002-2109-6465], Sinnott-Armstrong, Nasa A [0000-0003-4490-0601], Alonso, M Henar [0000-0003-0285-5451], Arndt, Volker [0000-0001-9320-8684], Bézieau, Stéphane [0000-0003-0095-1319], Bishop, D Timothy [0000-0002-8752-8785], Brezina, Stefanie [0000-0001-5238-6900], Buchanan, Daniel D [0000-0003-2225-6675], Chanock, Stephen J [0000-0002-2324-3393], de la Chapelle, Albert [0000-0001-9345-9248], Easton, Douglas F [0000-0003-2444-3247], Hampe, Jochen [0000-0002-2421-6127], Hayes, Richard B [0000-0002-0918-661X], Hofer, Philipp [0000-0003-2550-6019], Huang, Wen-Yi [0000-0002-4440-3368], Hudson, Thomas J [0000-0002-1376-4849], Jacobs, Eric J [0000-0002-8458-7659], Jenkins, Mark A [0000-0002-8964-6160], Joshi, Amit D [0000-0001-7581-6934], Küry, Sébastien [0000-0001-5497-0465], Larsson, Susanna C [0000-0003-0118-0341], Laurie, Cecelia A [0000-0001-6569-2501], Martín, Vicente [0000-0003-0552-2804], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger L [0000-0001-5764-7268], Naccarati, Alessio [0000-0001-5774-0905], Newcomb, Polly A [0000-0001-8786-0043], Pardini, Barbara [0000-0001-9571-4257], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul DP [0000-0001-8494-732X], Raskin, Leon [0000-0003-1195-7214], Rennert, Gad [0000-0002-8512-068X], Shin, Min-Ho [0000-0002-2217-5624], Toland, Amanda E [0000-0002-0271-1792], Vijai, Joseph [0000-0002-7933-151X], Weigl, Korbinian [0000-0003-4453-2036], Win, Aung Ko [0000-0002-2794-5261], Wolk, Alicja [0000-0001-7387-6845], Zheng, Wei [0000-0003-1226-070X], Bassik, Michael C [0000-0001-5185-8427], Moreno, Victor [0000-0002-2818-5487], Peters, Ulrike [0000-0001-5666-9318], and Apollo - University of Cambridge Repository
Subjects: Male, Nutrition and Disease, Colorectal cancer, IDENTIFIES 6, Genome-wide association study, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Genotype, ComputingMilieux_MISCELLANEOUS, Avaluació del risc per la salut, Genetics & Heredity, Genetics, 0303 health sciences, COLON-CANCER, 11 Medical And Health Sciences, Middle Aged, 3. Good health, Medical genetics, Female, RNA, Long Noncoding, Colorectal Neoplasms, Life Sciences & Biomedicine, Signal Transduction, EXPRESSION, medicine.medical_specialty, SUSCEPTIBILITY LOCI, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, Article, Health risk assessment, 03 medical and health sciences, QUALITY-CONTROL, Càncer colorectal, Journal Article, medicine, Life Science, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, VLAG, Aged, 030304 developmental biology, Global Nutrition, [SDV.GEN]Life Sciences [q-bio]/Genetics, Wereldvoeding, Science & Technology, ORGAN SIZE, MUTATIONS, Haplotype, Case-control study, 06 Biological Sciences, medicine.disease, Genetic architecture, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human genome, LYSOPHOSPHATIDIC ACID, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.
Published: 2018

17. Causal effects of lifetime smoking on breast and colorectal cancer risk:Mendelian randomization study

Author: Marc J. Gunter, Inger T. Gram, Elisabete Weiderpass, Hilary A. Tindle, Sun-Seog Kweon, Renée T. Fortner, Rudolf Kaaks, Sarah J Lewis, James Yarmolinsky, Stephen B. Gruber, Marije F. Bakker, Li Hsu, Yi Lin, Neil Murphy, Polly A. Newcomb, Konstantinos K. Tsilidis, Noralane M. Lindor, Rosario Tumino, Gianluca Severi, Hermann Brenner, Emmanouil Bouras, Jane C. Figueiredo, Niki Dimou, Richard M. Martin, Bethany Van Guelpen, María-José Sánchez-Pérez, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cancerfonden Cancer Research Foundation in Northern Sweden Deutsche Krebshilfe Vetenskapsrådet, VR Australian Lions Childhood Cancer Research Foundation, ALCCRF Knut och Alice Wallenbergs Stiftelse State of Maryland Vetenskapsrådet, VR: VR 2017-00650 Centers for Disease Control and Prevention, CDC Institut National Du Cancer, INCa National Institutes of Health, NIH National Cancer Institute, NCI: P30 CA015704 Centre Hospitalier Universitaire de Nantes, CHU de Nantes Conseil Régional des Pays de la Loire Association Anne de Bretagne Genetique Centre Hospitalier Universitaire de Nantes, CHU de Nantes U.S. Public Health Service, USPHS: HHSN261201500005C U.S. Department of Health and Human Services, HHS National Institutes of Health, NIH National Cancer Institute, NCI National Institute on Aging, NIA: U01 AG18033 Institut National Du Cancer, INCa: P30 CA006973, U01 CA86308 American Institute for Cancer Research, AICR European Commission, EC National Institutes of Health, NIH: R01 CA189184, 2P30CA015704-40, R01 CA207371, U01 CA206110 Matthias Lackas-Stiftung Johns Hopkins University, JHU: HHSN268201200008I National Cancer Institute, NCI National Institutes of Health, NIH: R01 CA143247, R01 CA81488, U01 CA122839, U19 CA148107, U01 CA167551 National Institutes of Health, NIH National Institute of Environmental Health Sciences, NIEHS: T32 ES013678 National Cancer Institute, NCI U.S. Department of Health and Human Services, HHS: R01 CA197350, R01 CA81488, R01 CA201407, P01 CA196569, U19 CA148107, P30 CA014089 Österreichische Forschungsförderungsgesellschaft, FFG: 829675 Instituto de Salud Carlos III, ISCIII European Regional Development Fund, ERDF: PI14-613, PI09-1286 Xarxa de Bancs de Tumors de Catalunya, XBTC: PT13/0010/0013 Generalitat de Catalunya: 2017SGR723 Junta de Castilla y León: LE22A10-2 Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR Ministerstvo Zdravotnictví Ceské Republiky, MZCR: AZV 17-30920A, AZV 15-27580A Grantová Agentura České Republiky, GA ČR: CZ GA CR: GAP304/10/1286, 1585 Deutsche Forschungsgemeinschaft, DFG: HO 5117/2-1, BR 1704/6-1, KL 2354/3-1, BR 1704/6-4, BR 1704/6-3, CH 117/1-1, HE 5998/2-1, RO 2270/8-1, BR1704/17-1 Bundesministerium für Bildung und Forschung, BMBF: 01ER0814, 01KH0404, 01ER0815, 01ER1505A, 01ER1505B U01 CA 84968-06 National Cancer Institute, NCI University of Maryland School of Public Health, SPH NIHR Imperial Biomedical Research Centre, BRC Imperial College London NIHR Imperial Biomedical Research Centre, BRC Centre International de Recherche sur le Cancer, CIRC Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A29017 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Vetenskapsrådet, VR Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Kræftens Bekæmpelse, DCS Associazione Italiana per la Ricerca sul Cancro, AIRC Instituto de Salud Carlos III, ISCIII Deutsches Krebsforschungszentrum, DKFZ Institut National de la Santé et de la Recherche Médicale, Inserm National Research Council, NRC Institut Gustave-Roussy Deutsches Krebsforschungszentrum, DKFZ Cancerfonden World Cancer Research Fund, WCRF Medical Research Council, MRC: MR/M012190/1 Generalitat de Catalunya: 2017SGR653, 2014SGR135, 2014SGR255, 2017SGR21 SAF2014-54453R, SAF07-64873, SAF 2010-19273 Xunta de Galicia: PGIDIT07PXIB9101209PR Instituto de Salud Carlos III, ISCIII European Regional Development Fund, ERDF: PS09/02368, PI14/00230, 17/00878, PI08/1276, PI17/00509, PI08/0024, PI11/00681, P111/00219, PI14/00173 Xarxa de Bancs de Tumors de Catalunya, XBTC: SLT002/ 16/00398 GCB13131592CAST European Cooperation in Science and Technology, COST: CA17118, BM1206 Deutsche Krebshilfe National Institutes of Health, NIH: K07 CA190673, P01 CA055075, K07CA190673, R35CA197735, U01 CA167552, UM1 CA167552, R01 CA042182, P01 CA087969, R01 CA151993, P50 CA127003, UM1 CA186107, R35 CA197735, R01 CA137178 HCRI15011-1 National Cancer Institute, NCI: R01CA136726 Damon Runyon Cancer Research Foundation, DRCRF: CI-8 Food Standards Agency, FSA Cancer Research UK, CRUK: C588/A19167 VicHealth Cancer Council Victoria National Health and Medical Research Council, NHMRC: 251553, 209057, 509348, 504711 National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: R01 CA81488 Florida Department of Health: 09BN-13 National Institutes of Health, NIH: R01 CA189184, P30 CA076292 National Institutes of Health, NIH: P30 DK034987, R01 CA66635 18226, 18223 Canadian Institutes of Health Research, CIHR: CRT 43821 National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: U01 CA74783 Cancerfonden Cancer Research Foundation, CRF Vetenskapsrådet, VR Australian Lions Childhood Cancer Research Foundation, ALCCRF Canadian Cancer Society National Institutes of Health, NIH: U01/ U24 CA074783, U01 CA167551 Pelotonia CA16058, CA67941 Canadian Institutes of Health Research, CIHR: 112746 Ontario Research Foundation, ORF: GL201-043 National Cancer Institute, NCI U.S. Department of Health and Human Services, HHS: U01 HG004446, GEI U01 HG 004438, Z01 CP 010200 Division of Cancer Epidemiology and Genetics, National Cancer Institute, DCEG Institut National Du Cancer, INCa National Institutes of Health, NIH Division of Cancer Prevention, National Cancer Institute, DCP, NCI National Institutes of Health, NIH: U24 CA074794, U01 CA074794, R01 CA076366, U01 CA167551 National Cancer Institute, NCI National Institutes of Health, NIH: UM1 CA182883, U10 CA37429 National Cancer Institute, NCI Institut National Du Cancer, INCa: R03 CA153323, P01 CA074184, K05 CA152715, R01 CA097325 National Institutes of Health, NIH: KL2 TR000421 National Center for Advancing Translational Sciences, NCATS Stockholms Läns Landsting Vetenskapsrådet, VR: K2015-55X-22674-01-4, K2008-55X-20157-03-3, K2006-72X-20157-01-2 Karolinska Institutet, KI National Institutes of Health, NIH: K05 CA154337 Swedish Cancer Foundation National Heart, Lung, and Blood Institute, NHLBI National Institutes of Health, NIH U.S. Department of Health and Human Services, HHS: HHSN268201100004C, HHSN268201100003C, HHSN268201100001C, HHSN271201100004C, HHSN268201100046C, HHSN268201100002C, R.M. Martin reports grants from Cancer Research UK during the conduct of the study. R.T. Fortner reports that grants from German Cancer Aid and from German Ministry of Education and Research supported the conduct of EPIC Heidelberg. S.B. Gruber reports other from Brogent International LLC outside the submitted work. B. van Guelpen reports grants from Swedish Research Council, Swedish Cancer Society, Knut and Alice Wallenberg Foundation, Lion’s Cancer Research Foundation at Umea° University, and Cancer Research Foundation in Northern Sweden during the conduct of the study. No disclosures were reported by the other authors., CLUE: We appreciate the continued efforts of the staff members at the Johns Hopkins George W. Comstock Center for Public Health Research and Prevention in the conduct of the CLUE II study. We thank the participants in CLUE. Cancer incidence data for CLUE were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Maryland Department of Health, 201 W. Preston Street, Room 400, Baltimore, MD 21201, http://phpa.dhmh.maryland.gov/cancer, 410-767-4055. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data., CPS-II: The authors thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program., NSHDS investigators thank the Biobank Research Unit at Umea° University, the V€asterbotten Intervention Programme, the Northern Sweden MONICA study and Region V€asterbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council (VR 2017-00650)., Cancer incidence data have been provided by the District of Columbia Cancer Registry, Georgia Cancer Registry, Hawaii Cancer Registry, Minnesota Cancer Surveillance System, Missouri Cancer Registry, Nevada Central Cancer Registry, Pennsylvania Cancer Registry, Texas Cancer Registry, Virginia Cancer Registry, and Wisconsin Cancer Reporting System. All are supported in part by funds from the Center for Disease Control and Prevention, National Program for Central Registries, local states or by the National Cancer Institute, Surveillance, Epidemiology, and End Results program. The results reported here and the conclusions derived are the sole responsibility of the authors., Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088, R01 CA059045, R01CA201407). This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704., ASTERISK: a Hospital Clinical Research Program (PHRC-BRD09/C) from the University Hospital Center of Nantes (CHU de Nantes) and supported by the Regional Council of Pays de la Loire, the Groupement des EntreprisesFranc¸aises dans la Luttecontre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue RégionaleContre le Cancer (LRCC)., The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services., CLUE funding was from the National Cancer Institute (U01 CA86308, Early Detection Research Network, and P30 CA006973), National Institute on Aging (U01 AG18033), and the American Institute for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. COLO2&3: NIH (R01 CA60987).
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Epidemiology, medicine.drug_class, Colorectal cancer, Breast Neoplasms, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, Mendelian randomization, Genetic predisposition, Humans, Medicine, Risk factor, 11 Medical and Health Sciences, business.industry, Smoking, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Confidence interval, 3. Good health, Causality, 030104 developmental biology, Estrogen, 030220 oncology & carcinogenesis, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ICEP, Colorectal Neoplasms, business, Genome-Wide Association Study
Abstract: Background: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer. Methods: Genome-Wide Association Study summary data were used to identify genetic variants associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/105,974 controls) and colorectal cancer (52,775 cases/45,940 controls). Results: In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-SD increment: 1.13; 95% confidence interval (CI): 1.00–1.26; P = 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor–positive and estrogen receptor–negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer (OR per 1-SD increment, 1.21; 95% CI, 1.04–1.40; P = 0.01), colon cancer (OR, 1.31; 95% CI, 1.11–1.55; P < 0.01), and rectal cancer (OR, 1.36; 95% CI, 1.07–1.73; P = 0.01). Ever having smoked regularly was not associated with risks of breast (OR, 1.01; 95% CI, 0.90–1.14; P = 0.85) or colorectal cancer (OR, 0.97; 95% CI, 0.86–1.10; P = 0.68). Conclusions: These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer. Impact: The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.
Published: 2021

18. Life-course socioeconomic disadvantage and lung function: a multicohort study of 70 496 individuals

Author: Carla Moreira, Graham G. Giles, Alexandra Lenoir, Silvia Stringhini, Peter Vollenweider, Paolo Vineis, Vânia Rocha, Henrique Barros, Marcel Goldberg, Andrew Steptoe, Mika Kivimäki, Sílvia Fraga, Cristian Carmeli, Marie Zins, ISPUP-EPIUnit [Porto, Portugal], Universidade do Porto = University of Porto, University of Minho [Braga], Université de Fribourg = University of Fribourg (UNIFR), Lausanne University Hospital, University College of London [London] (UCL), Cancer Council Victoria [Melbourne, VIC, Australia], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Descartes, Sorbonne Paris Cité, Imperial College London, Université de Lausanne = University of Lausanne (UNIL), Geneva University Hospital (HUG), This work was supported by European regional development fund through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology (FCT, Portuguese Ministry of Science, Technology and Higher Education) under the EPIUnit, Instituto de Saúde Pública da Universidade do Porto, Portugal (POCI-01-0145-FEDER-006862, reference: UID/DTP/04750/2019). It is also supported by the European Commission (Horizon 2020 grant number 633666), PhD grant SFRH/BD/103726/ 2014 (V. Rocha) co-funded by FCT and the POCH/FSE Program, FCT contract CEECIND/01516/2017/CP1406/CT0001 (S. Fraga), and by the University of Lausanne (Pro-Femmes grant, S. Stringhini). M. Kivimaki was supported by the Medical Research Council (K013351, R024227), the US National Institute on Aging (R01AG056477), NordForsk, the Academy of Finland (311492), and Helsinki Institute of Life Science during the conduct of the study. The CoLaus|PsyCoLaus study is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 3200B0_105993, 3200B0_118308, 33CSCO_122661, 33CS30_139468 and 33CS30_14840). The Constances cohort is supported by the Caisse nationale d’assurance maladie and by a grant from the Agence nationale de la recherche (ANR-11-INBS-0002). Funding information for this article has been deposited with the Crossref Funder Registry., Jan Alberts, Harri Alenius, Mauricio Avendano, Laura Baglietto, Valeria Baltar, Henrique Barros, Mel Bartley, Michele Bellone, Eloise Berger, David Blane, Murielle Bochud, Giulia Candiani, Cristian Carmeli, Luca Carra, Raphaele Castagne, Marc Chadeau-Hyam, Sergio Cima, Giuseppe Costa, Emilie Courtin, Cyrille Delpierre, Angelo D'Errico, Angela Donkin, Pierre-Antoine Dugue, Paul Elliott, Guy Fagherazzi, Giovanni Fiorito, Silvia Fraga, Martina Gandini, Valérie Gares, Pascale Gerbouin-Rerolle, Graham Giles, Marcel Goldberg, Dario Greco, Allison Hodge, Maryam Karimi, Piia Karisola, Michelle Kelly-Irving, Mika Kivimaki, Jessica Laine, Thierry Lang, Audrey Laurent, Richard Layte, Benoit Lepage, Dori Lorsch, Giles Machell, Johan Mackenbach, Michael Marmot, Cathal McCrory, Carlos de Mestral, Cynthia Miller, Roger Milne, Peter Muennig, Wilma Nusselder, Dusan Petrovic, Lourdes Pilapil, Silvia Polidoro, Martin Preisig, Ana Isabel Ribeiro, Fulvio Ricceri, Paolo Recalcati, Erica Reinhard, Oliver Robinson, Jose Rubio Valverde, Severine Saba, Frank Santegoets, Gianluca Severi, Terrence Simmons, Silvia Stringhini, Adam Tabak, Vesa Terhi, Joannie Tieulent, Salvatore Vaccarella, Federica Vigna-Taglianti, Paolo Vineis, Peter Vollenweider, Marie Zins, European Project: 633666,H2020,H2020-PHC-2014-two-stage,LIFEPATH(2015), Instituto de Saúde Pública da Universidade do Porto, University of Fribourg, Demarquay, Sandrine, and Lifecourse biological pathways underlying social differences in healthy ageing - LIFEPATH - - H20202015-05-01 - 2019-04-30 - 633666 - VALID
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Vital capacity, [SDV]Life Sciences [q-bio], Vital Capacity, 030204 cardiovascular system & hematology, Lung, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Risk Factors, Forced Expiratory Volume, medicine, Humans, 030212 general & internal medicine, Socioeconomic status, Aged, ddc:616, business.industry, Middle Aged, respiratory system, medicine.disease, Obesity, respiratory tract diseases, Respiratory Function Tests, Disadvantaged, [SDV] Life Sciences [q-bio], Institutional repository, medicine.anatomical_structure, Socioeconomic Factors, Life course approach, Female, business, Demography
Abstract: Background Lung function is an important predictor of health and a marker of physical functioning at older ages. This study aimed to quantify the years of lung function lost according to disadvantaged socioeconomic conditions across the life-course. Methods This multicohort study used harmonised individual-level data from six European cohorts with information on life-course socioeconomic disadvantage and lung function assessed by forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). 70 496 participants (51% female) aged 18–93 years were included. Socioeconomic disadvantage was measured in early life (low paternal occupational position), early adulthood (low educational level) and adulthood (low occupational position). Risk factors for poor lung function (e.g. smoking, obesity, sedentary behaviour, cardiovascular and respiratory diseases) were included as potential mediators. The years of lung function lost due to socioeconomic disadvantage were computed at each life stage. Results Socioeconomic disadvantage during the life-course was associated with a lower FEV1. By the age of 45 years, individuals experiencing disadvantaged socioeconomic conditions had lost 4–5 years of healthy lung function versus their more advantaged counterparts (low educational level −4.36 (95% CI −7.33–−2.37) for males and −5.14 (−10.32–−2.71) for females; low occupational position −5.62 (−7.98–−4.90) for males and −4.32 (−13.31–−2.27) for females), after accounting for the risk factors for lung function. By the ages of 65 years and 85 years, the years of lung function lost due to socioeconomic disadvantage decreased by 2–4 years, depending on the socioeconomic indicator. Sensitivity analysis using FVC yielded similar results to those using FEV1. Conclusion Life-course socioeconomic disadvantage is associated with lower lung function and predicts a significant number of years of lung function loss in adulthood and at older ages. This work was supported by European regional development fund through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology (FCT; Portuguese Ministry of Science, Technology and Higher Education) under the EPIUnit, Instituto de Saúde Pública da Universidade do Porto, Portugal (POCI-01-0145-FEDER-006862; reference: UID/DTP/04750/2019). It is also supported by the European Commission (Horizon 2020 grant number 633666), PhD grant SFRH/BD/103726/2014 (V. Rocha) co-funded by FCT and the POCH/FSE Program, FCT contract info:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND/01516/2017/CP1406/CT0001/PT/CP1406/CT0001 (S. Fraga), and by the University of Lausanne (Pro-Femmes grant, S. Stringhini). M. Kivimaki was supported by the Medical Research Council (K013351, R024227), the US National Institute on Aging (R01AG056477), NordForsk, the Academy of Finland (311492), and Helsinki Institute of Life Science during the conduct of the study. The CoLaus|PsyCoLaus study is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 3200B0_105993, 3200B0_118308, 33CSCO_122661, 33CS30_139468 and 33CS30_14840). The Constances cohort is supported by the Caisse nationale d'assurance maladie and by a grant from the Agence nationale de la recherche (ANR-11-INBS-0002). Funding information for this article has been deposited with the Crossref Funder Registry.
Published: 2021

19. Research on environmental exposure to noise and risk of cardiometabolic diseases (type 2 diabetes, hypertension, cardiovascular diseases) through devices connected to the E3N-E4N cohort in Ile-de-France and Auvergne Rhône-Alpes (2000-2018) - France

Author: Faure, Elodie, Evrard, Anne-Sophie, Vincent, Bruno, Mietlicki, Fanny, Fagherazzi, Guy, Severi, Gianluca, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Bruitparif, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Luxembourg Institute of Health (LIH), Cancer Epidemiology Centre, Cancer Council Victoria, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS.MECA.VIBR]Physics [physics]/Mechanics [physics]/Vibrations [physics.class-ph], E-Heatlh device, EPIDEMIOLOGY, 3. Good health, NOISE, CARDIO-METABOLIC DISEASES, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph]
Abstract: International audience; The World Health Organization's (WHO) guidelines for environmental noise (2018) outline the evidence on the health effects of transport noise. The main associated effects are annoyance, sleep disturbance or cardiovascular diseases (CVD). We are currently implementing a project called "BROUHAHA", which will aim to study the association between exposure to transport noise and the risk of cardiometabolic diseases: type 2 diabetes, hypertension or CVD. Component A will be conducted with 35,000 women from the E3N cohort (www.e3n.fr) who resided in Ile-de-France (IdF) or Auvergne Rhône-Alpes (AuRA) (2000-2018). The second component B will be a pilot study conducted with 240 subjects from the E4N (www.e4n.fr) cohort residing in IdF or AuRA. The objective will be to study the effects of short-term noise exposure on heart rate, sleep parameters, hypertension and glycemia. Acoustic and physiological parameters will be measured via an e-health device. This multidisciplinary project is in accordance with WHO recommendations and with the 2002/49/EC Directive on the assessment and management of environmental noise. BROUHAHA will make it possible to complete scientific knowledge on health-related exposure to transport noise and to adapt public health policies in this field.
Published: 2020

20. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author: Daniel R. Barnes, Matti A. Rookus, Lesley McGuffog, Goska Leslie, Thea M. Mooij, Joe Dennis, Nasim Mavaddat, Julian Adlard, Munaza Ahmed, Kristiina Aittomäki, Nadine Andrieu, Irene L. Andrulis, Norbert Arnold, Banu K. Arun, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel Barrowdale, Javier Benitez, Pascaline Berthet, Katarzyna Białkowska, Amie M. Blanco, Marinus J. Blok, Bernardo Bonanni, Susanne E. Boonen, Åke Borg, Aniko Bozsik, Angela R. Bradbury, Paul Brennan, Carole Brewer, Joan Brunet, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Lise Lotte Christensen, Wendy K. Chung, Kathleen B.M. Claes, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Antonis Antoniou, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D. Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-ren Ong, Lucy Side, Aoife O’Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Mary B. Daly, Miguel de la Hoya, Robin de Putter, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Cecilia M. Dorfling, Martine Dumont, Bent Ejlertsen, Christoph Engel, Lenka Foretova, Florentia Fostira, Michael Friedlander, Eitan Friedman, Patricia A. Ganz, Judy Garber, Andrea Gehrig, Anne-Marie Gerdes, Paul Gesta, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Anna González-Neira, Mark H. Greene, Daphne Gschwantler-Kaulich, Eric Hahnen, Ute Hamann, Julia Hentschel, Frans B.L. Hogervorst, Maartje J. Hooning, Judit Horvath, Chunling Hu, Peter J. Hulick, Evgeny N. Imyanitov, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Catherine Noguès, Claudine Isaacs, Angel Izquierdo, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Esther M. John, Vijai Joseph, Beth Y. Karlan, Karin Kast, Torben A. Kruse, Ava Kwong, Yael Laitman, Conxi Lazaro, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Jennifer T. Loud, Jan Lubiński, Phuong L. Mai, Siranoush Manoukian, Hanne E.J. Meijers-Heijboer, Alfons Meindl, Arjen R. Mensenkamp, Austin Miller, Marco Montagna, Semanti Mukherjee, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Dieter Niederacher, Finn Cilius Nielsen, Liene Nikitina-Zake, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Claus-Eric Ott, Laura Papi, Sue K. Park, Michael T. Parsons, Inge Sokilde Pedersen, Bernard Peissel, Ana Peixoto, Paolo Peterlongo, Georg Pfeiler, Karolina Prajzendanc, Miquel Angel Pujana, Paolo Radice, Juliane Ramser, Susan J. Ramus, Johanna Rantala, Gad Rennert, Harvey A. Risch, Mark Robson, Karina Rønlund, Ritu Salani, Leigha Senter, Payal D. Shah, Priyanka Sharma, Lucy E. Side, Christian F. Singer, Thomas P. Slavin, Penny Soucy, Melissa C. Southey, Amanda B. Spurdle, Doris Steinemann, Zoe Steinsnyder, Christian Sutter, Yen Yen Tan, Manuel R. Teixeira, Soo Hwang Teo, Darcy L. Thull, Silvia Tognazzo, Amanda E. Toland, Alison H. Trainer, Nadine Tung, Elizabeth J. van Rensburg, Ana Vega, Jeroen Vierstraete, Gabriel Wagner, Shan Wang-Gohrke, Barbara Wappenschmidt, Jeffrey N. Weitzel, Siddhartha Yadav, Xin Yang, Drakoulis Yannoukakos, Dario Zimbalatti, Kenneth Offit, Mads Thomassen, Fergus J. Couch, Rita K. Schmutzler, Jacques Simard, Douglas F. Easton, Antonis C. Antoniou, Pediatric surgery, Human genetics, CCA - Cancer biology and immunology, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Chapel Allerton Hospital, Great Ormond Street Hospital for Children [London] (GOSH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto (University of Toronto), Christian-Albrechts University of Kiel, The University of Texas M.D. Anderson Cancer Center [Houston], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], CIBER de Enfermedades Raras (CIBERER), Spanish National Cancer Research Center (CNIO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Pomeranian Medical University [Szczecin] (PUM), University of California (UC), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], European Institute of Oncology IRCCS [Milan, Italy] (EIO), Zealand University Hospital [Roskilde, Denmark], Lund University [Lund], National Institute of Oncology [Budapest, Hungary], Abramson Cancer Center [philadelphia], University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Institute of Genetic Medicine [Newcastle], Newcastle University [Newcastle], Royal Devon & Exeter Hospital, Exeter, UK, Catalan Institute of Oncology [Barcelone, Espagne], Huntsman Cancer Institute [Salt Lake City], University of Utah, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Pisa University Hospital, Peter MacCallum Cancer Centre [Melbourne, Australie], University of Melbourne, Aarhus University Hospital, Columbia University [New York], Ghent University Hospital, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Sheffield Children's NHS Foundation Trust, Fox Chase Cancer Center, Queen Elizabeth University Hospital (Glasgow), Centre hospitalier universitaire de Nantes (CHU Nantes), Leiden University Medical Center (LUMC), Beckman Research Institute of the City of Hope, Abramson Cancer Center, University of Pretoria [South Africa], Centre Hospitalier Universitaire de Québec Research Center [Canada], Royal Marsden NHS Foundation Trust, Copenhagen University Hospital, Leipzig University, University of Manchester [Manchester], Manchester Academic Health Science Centre (MAHSC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Masaryk Memorial Cancer Institute (MMCI), Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research 'Demokritos' (NCSR), NHMRC Clinical Trials Centre [Camperdown NSW 2050, Australie], Chaim Sheba Medical Center, Tel Aviv University (TAU), Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Dana-Farber Cancer Institute [Boston], University of Würzburg, Rigshospitalet [Copenhagen], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Hospices Civils de Lyon (HCL), University of Kansas [Kansas City], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Medizinische Universität Wien = Medical University of Vienna, University of Cologne, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Lancashire NHS Foundation Trust, University Hospital Leipzig, Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Mayo Clinic, NorthShore University HealthSystem [Evanston, IL, USA], The University of Chicago Medicine [Chicago], N. N. Petrov Institute of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Guy's and St Thomas' NHS Foundation Trust [London, UK], Peter MacCallum Cancer Center, East Melbourne, Peter MacCallum Cancer Center, Vilnius University [Vilnius], The State Scientific Research Institute Nature Research Centre, Vilnius, Lithuania, Stanford University School of Medicine [CA, USA], Memorial Sloane Kettering Cancer Center [New York], Cedars-Sinai Medical Center, Technische Universität Dresden = Dresden University of Technology (TU Dresden), University Medical Center [Utrecht], Odense University Hospital [Odense, Denmark], The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Hong Kong Sanatorium and Hospital [Hong Kong] (HKSH), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], Fondation MINES ParisTech, Karolinska Institutet [Stockholm], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Amsterdam UMC - Amsterdam University Medical Center, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Radboud University Medical Center [Nijmegen], Roswell Park Cancer Institute [Buffalo], Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], University of Toronto, University Health Network, University Hospital Düsseldorf, Latvian Biomedical Research and Study Centre [Rīga], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Chicago, Birmingham Women's and Children's NHS Foundation Trust, Cambridge University Hospitals - NHS (CUH), Charité Campus Virchow-Klinikum (CVK), Università degli Studi di Firenze = University of Florence (UniFI), Seoul National University College of Medicine [Séoul, Corée du Sud] (SNUCM), Seoul National University [Seoul] (SNU), QIMR Berghofer Medical Research Institute, Aalborg University [Denmark] (AAU), IRCCS Istituto Nazionale dei Tumori [Milano], Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Klinikum rechts der Isar [Munich, Germany], University of New South Wales [Sydney] (UNSW), Garvan Institute of medical research, Technion Faculty of Medicine [Haifa, Israel], Yale School of Medicine [New Haven, Connecticut] (YSM), Vejle Hospital [Danemark], Ohio State University [Columbus] (OSU), Centre de lutte contre le cancer Paul-Strauss, Institut de Cancérologie de Strasbourg Europe (ICANS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Kansas Medical Center [Kansas City, KS, USA], Princess Anne Hospital, City of Hope Comprehensive Cancer Center [Duarte], Monash University [Clayton], Cancer Council Victoria [Melbourne, VIC, Australia], Hannover Medical School [Hannover] (MHH), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Heidelberg University Hospital [Heidelberg], Institute of Biomedical Sciences Abel Salazar - ICBAS [Porto, Portugal], Malaysia and University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya [Kuala Lumpur, Malaisie], University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), McGill University = Université McGill [Montréal, Canada], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), Instituto de Investigaciones Sanitarias, Universidade de Santiago de Compostela [Spain] (USC ), Universiteit Gent = Ghent University (UGENT), Oxford University Hospitals NHS Trust, University of Oxford, Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital of Cologne [Cologne], Mayo Clinic [Rochester], Collaborators : Pascaline Berthet, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Julian Adlard, Munaza Ahmed, Antonis Antoniou, Daniel Barrowdale, Paul Brennan, Carole Brewer, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-Ren Ong, Lucy Side, Aoife O'Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Peter Devilee, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Nadine Andrieu, Catherine Noguès, Dupuis, Christine, Institut Català de la Salut, [Barnes DR, McGuffog L, Leslie G, Dennis J] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Rookus MA, Mooij TM] The Netherlands Cancer Institute, Department of Epidemiology (PSOE), Amsterdam, The Netherlands. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Barnes, Daniel [0000-0002-3781-7570], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Mavaddat, Nasim [0000-0003-0307-055X], RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI), Medical Oncology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, Helsinki University Hospital Area, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, University of Helsinki, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Pomeranian Medical University, University of California, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], University of Leipzig [Leipzig, Allemagne], Masaryk Memorial Cancer Institute (RECAMO), Tel Aviv University [Tel Aviv], University of California-University of California, University of Münster, Amsterdam UMC, Technical University of Munich (TUM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Garvan Institute of Medical Research [Sydney, Australia], Yale University School of Medicine, Vejle Hospital, University of Kansas Medical Center [Lawrence], Université Paris Descartes (Paris 5), University of Malaya [Kuala Lumpur, Malaisie], Universiteit Gent = Ghent University [Belgium] (UGENT), and University of Oxford [Oxford]
Subjects: 0301 basic medicine, Oncology, endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], [SDV]Life Sciences [q-bio], Càncer d'ovari, Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], MODIFIERS, Diàtesi, SUSCEPTIBILITY, Carcinoma, Ovarian Epithelial, PRS, 0302 clinical medicine, Breast cancer, 3123 Gynaecology and paediatrics, Risk Factors, Medicine and Health Sciences, Medicine, Genetics(clinical), genetics, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Genetics (clinical), Ovarian Neoplasms, education.field_of_study, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], BRCA1 Protein, Hazard ratio, Absolute risk reduction, 1184 Genetics, developmental biology, physiology, article, ASSOCIATION, neoplasias::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas::carcinoma epitelial de ovario [ENFERMEDADES], ddc, 3. Good health, [SDV] Life Sciences [q-bio], ovarian cancer, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Heterozygote, Population, 3122 Cancers, Single-nucleotide polymorphism, Breast Neoplasms, MUTATION CARRIERS, Ovaris - Càncer - Aspectes genètics, Càncer de mama, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, Ovarian cancer, BRCA1/2, Internal medicine, Humans, Genetic Predisposition to Disease, education, Retrospective Studies, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], BRCA2 Protein, IDENTIFICATION, business.industry, Neoplasms::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms::Carcinoma, Ovarian Epithelial [DISEASES], Retrospective cohort study, ALLELES, medicine.disease, BRCA1, BRCA2, MODEL, PATHOLOGY, 030104 developmental biology, Mutation, Mama - Càncer - Aspectes genètics, 3111 Biomedicine, business
Abstract: Contains fulltext : 229292.pdf (Publisher’s version ) (Open Access) PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10(-72)). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10(-22)) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10(-12)) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
Published: 2020

21. Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses

Author: Elio Riboli, Jochen Hampe, Ruth C. Travis, Andrea N. Burnett-Hartman, Anna H. Wu, Steven Gallinger, Stephen B. Gruber, Christopher I. Li, Bethany Van Guelpen, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Demetrius Albanes, Jeroen R. Huyghe, Lori C. Sakoda, Jennifer Ose, Daniel D. Buchanan, Kenneth Offit, D. Timothy Bishop, John D. Potter, Sonja I. Berndt, Neil Murphy, Vittorio Perduca, Roger L. Milne, Niki Dimou, Marc J. Gunter, Ulrike Peters, Wen Yi Huang, Sergi Castellví-Bel, Graham Casey, Robert E. Schoen, Martha L. Slattery, Kathryn E. Bradbury, Albert de la Chapelle, Temitope O. Keku, Andrea Gsur, Wei Zheng, Gad Rennert, Hermann Brenner, Tabitha A. Harrison, Claudia Agnoli, Fränzel J.B. Van Duijnhoven, Sabina Rinaldi, Catherine M. Tangen, Jane C. Figueiredo, Ludmila Vodickova, Andrew T. Chan, Tilman Kühn, Hansong Wang, Mingyang Song, Sun-Seog Kweon, Annika Lindblom, Amanda I. Phipps, Cornelia M. Ulrich, Victor Moreno, Mark A. Jenkins, Li Hsu, Emily White, Conghui Qu, Peter T. Campbell, Stéphane Bézieau, Nikos Papadimitriou, Michael O. Woods, Jelena Bešević, Polly A. Newcomb, Pavel Vodicka, Heather Hampel, Barbara L. Banbury, Amanda J. Cross, Robert Carreras-Torres, Alicja Wolk, Graham G. Giles, Michael Hoffmeister, Elizabeth A. Platz, N. Charlotte Onland-Moret, Dallas R. English, Li Li, Jenny Chang-Claude, Vicente Martín, Richard M. Martin, María Dolores Chirlaque, Konstantinos K. Tsilidis, Clemens Schafmayer, Shuji Ogino, Nutrition and Metabolism Section, International Agency for Research on Cancer, Centre international de Recherche sur le Cancer (CIRC), School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], International Agency for Cancer Research (IACR), School of Public Health [London, UK] (Faculty of Medicine), Candiolo Cancer Institute (IRCCS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Interactions récepteurs ligands en immunocancérologie et immunopathologie, IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), St. James's University Hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University Medical Center [Utrecht], The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Department of Preventive Medicine, University of Southern California (USC), Division of Cancer Epidemiology, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Ohio State University [Columbus] (OSU), Cancer Epidemiology Centre, Cancer Council Victoria, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), FESTO, Universität Stuttgart [Stuttgart], Division of Cancer Epidemiology and Genetics, Department of Medical Genetics, HMNC Brain Health, University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Dell-EMC, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], and Center for Astrophysical Sciences [Baltimore]
Subjects: Oncology, Male, Nutrition and Disease, Colorectal cancer, BMI, body mass index, PLASMA-INSULIN, IGFBP3, IGF1, insulin-like growth factor 1, Genome-wide association study, GWAS, genome-wide association studies, MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, FACTOR (IGF)-I, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Insulina, Medicine, Insulin, GWAS, Registries, Insulin-Like Growth Factor I, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, ICC, intraclass correlation coefficient, Incidence, Hazard ratio, MR, Mendelian randomization, Gastroenterology, MEN, SNP, single nucleotide polymorphism, Middle Aged, SERUM-LEVELS, 3. Good health, IGF-I, CRC, 030220 oncology & carcinogenesis, CRP, C-reactive protein, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Medical Genetics, REGRESSION DILUTION, Signal Transduction, medicine.medical_specialty, HbA1c, glycolated hemoglobin, FACTOR-I, Polymorphism, Single Nucleotide, Risk Assessment, Article, C-PEPTIDE, 03 medical and health sciences, Sex Factors, Insulin-Like Growth Factor II, Càncer colorectal, Internal medicine, COLON, Mendelian randomization, Biomarkers, Tumor, Journal Article, Humans, IGFBP3, insulin-like growth factor binding protein 3, 030304 developmental biology, Aged, VLAG, Medicinsk genetik, Cancer och onkologi, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Case-control study, Cancer, IGFBP-3, 1103 Clinical Sciences, Odds ratio, Mendelian Randomization Analysis, medicine.disease, HR, hazard ratio, United Kingdom, CI, confidence interval, OR, odds ratio, Insulin-Like Growth Factor Binding Protein 3, Case-Control Studies, Cancer and Oncology, SHBG, sex hormone binding globulin, 1114 Paediatrics and Reproductive Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, SD, standard deviation, 1109 Neurosciences, Follow-Up Studies
Abstract: Background & Aims Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. Methods Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) Results After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. Conclusions In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis., Graphical abstract
Published: 2020

22. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author: Eduardo Nagore, Caroline Hayward, Christopher I. Amos, Douglas F. Easton, Zaida García-Casado, Julie Lang, Anjali K. Henders, Veronica Höiom, Lisa Bowdler, Kathryn P. Burdon, Laura Del Regno, Nick Orr, Per Arne Andresen, Tongwu Zhang, Rose Yang, Myriam Brossard, Eric K. Moses, Dirk Schadendorf, Laura Cattaneo, Casey Rowe, Essen-Heidelberg Investigators, Hans-Joachim Schulze, Jamie E Craig, D. Timothy Bishop, Anne E. Cust, Johan Hansson, David E. Elder, Nelleke A. Gruis, Donato Calista, Wei V. Chen, Abrar A. Qureshi, Amy Hutchinson, Pilar Galan, Leanne Wallace, Jennifer H. Barrett, Nilesh J. Samani, Maria Teresa Landi, Per Helsing, Andreas Hadjisavvas, Fengju Song, Celia Requena, Elizabeth M. Gillanders, Arantxa Rodriguez, Joan Anton Puig-Butille, Blair H. Smith, Mark Smithers, Michael Malasky, Marianna Sanna, Miriam Potrony, Maria A. Loizidou, Evangelos Evangelou, Richard A. Scolyer, Karen A. Pooley, Rachel E. Neale, Mario Falchi, Adèle C. Green, Monica Rodolfo, Ketty Peris, Licia Rivoltini, Mark M. Iles, Catherine M. Olsen, Alexander J. Stratigos, Tadeusz Dębniak, Weiyin Zhou, H. Peter Soyer, Xin Li, Margaret A. Tucker, Rajesh Kumar, Håkan Olsson, Anders Molven, Nicholas G. Martin, Anthony J. Swerdlow, Aurelie Vogt, Lars A. Akslen, Stuart MacGregor, Sarah V. Ward, Hamida Mohamdi, Bruna Dalmasso, Grant W. Montgomery, Rona M. MacKie, Esther Azizi, Gonçalo R. Abecasis, Chiara Menin, Alison M. Dunning, Ibd investigators, Kevin M. Brown, Jiali Han, Veryan Codd, Graham J. Mann, Nicholas K. Hayward, Marko Hočevar, Eitan Friedman, Richard A. Sturm, Paola Queirolo, Qtwin Investigators, Lawrie Wheeler, Lars G. Fritsche, Shenying Fang, Kiarash Khosrotehrani, Nicole A Kukutsch, Pol Gimenez-Xavier, Belynda Hicks, Matthew Zawistowski, Alessia Visconti, Jessica Harris, Chad M. Brummett, Paola Ghiorzo, andMe, David G. Hunter, Veronique Bataille, Julia Newton-Bishop, Srdjan Novaković, Amfs Investigators, Siranoush Manoukian, Jianxin Shi, Mitchell J. Machiela, G. Mark Lathrop, Josep Malvehy, Katerina P. Kypreou, Susana Puig, Dale R. Nyholt, I. Stefanaki, Maria Concetta Fargnoli, Lisa A. Simms, Kerrie McAloney, M. Malt, Adam J. Trower, Matthew Law, Lei Song, Paul D.P. Pharoah, Christian Ingvar, Jiyeon Choi, Alisa M. Goldstein, Jeffrey E. Lee, Mark Harland, Cristina Pellegrini, Daniela Massi, Sarah Simi, Scott D. Gordon, Jacobo Martinez, Florence Demenais, Kristine Jones, Graham L. Radford-Smith, David C. Whiteman, Lorenza Pastorino, Lisa Elefanti, Arcangela De Nicolo, Mario Mandalà, Juliette Randerson-Moor, Q-Mega, Jan Lubinski, Stephen J. Chanock, Marie-Françoise Avril, David L. Duffy, Helen Gogas, Nienke van der Stoep, Peter A. Kanetsky, Georgina V. Long, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), University of Leeds, QIMR Berghofer Medical Research Institute, National and Kapodistrian University of Athens (NKUA), Ospedale Policlinico San Martino [Genoa], Universita degli studi di Genova, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Maurizio Bufalini Hospital, University of L'Aquila [Italy] (UNIVAQ), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Cyprus Institute of Neurology and Genetics, University of Athens Medical School [Athens], The University of Sydney, Universitat de Barcelona (UB), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], University of Michigan [Ann Arbor], University of Michigan System, Instituto Valenciano de Oncologia, Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], IRCCS Istituto Nazionale dei Tumori [Milano], Ninewells Hospital and Medical School [Dundee], Cyprus Institute (CyI), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Queensland [Brisbane], Haukeland University Hospital, University of Bergen (UiB), Geisel School of Medicine at Dartmouth, Oslo University Hospital [Oslo], Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], King‘s College London, Menzies School of Health Research [Australia], Charles Darwin University, The University of Texas M.D. Anderson Cancer Center [Houston], University of Leicester, Flinders University [Adelaide, Australia], West Pomeranian University of Technology Szczecin, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Human Genome Research Institute (NHGRI), Leiden University Medical Center (LUMC), Karolinska Institutet [Stockholm], Queensland University of Technology [Brisbane] (QUT), Institute of Oncology Ljubljana, Harvard T.H. Chan School of Public Health, Lund University [Lund], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Glasgow, Statistical Genetics, and Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH) United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAU19CA148112SEARCH team (Cancer Research UK) C490/A16561AOCS (US Army Medical Research and Material Command) DAMD17-01-1-0729Canadian Institutes of Health Research (CIHR)Cancer Council Victoria Queensland Cancer Fund Cancer Council New South Wales Cancer Council South Australia Cancer Council Western Australia Cancer Council Tasmania National Health and Medical Research Council of AustraliaID400413ID400281National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS Ministry of Health, Italy Associazione Italiana per la Ricerca sul Cancro (AIRC)IG 15460Spanish Fondo de Investigaciones Sanitarias grant - FEDER 'Una manera de hacer Europa' PI15/00716PI15/00956CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain - European Development Regional Fund 'A way to achieve Europe' ERDF AGAUR of the Catalan Government, Spain 2014_SGR_603European CommissionEuropean Commission Joint Research CentreLSHC-CT-2006-018702European Union (EU) 'Fundacio La Marato de TV3', Catalonia, Spain 201331-30'Fundacion Cientifica de la Asociacion Espanola Contra el Cancer', Spain GCB15152978SOENCERCA Programme/Generalitat de Catalunya Italian Ministry of the University and Scientific Research (PRIN-2012 grant) 2012JJX494Melanoma Research Alliance United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI)CA88363CA83115CA122838CA87969CA055075CA100264CA133996CA49449National Health and Medical Research Council of Australia200071241944339462380385389927389875389891389892389938443036442915442981496610496675496739552485552498APP1049894Cancer Council Queensland Cancer Institute New South Wales Australian GovernmentDepartment of Industry, Innovation and ScienceCooperative Research Centres (CRC) Programme Australian Cancer Research Foundation Wellcome TrustWT084766/Z/08/ZNational Health and Medical Research Council of Australia Australian Research Council Department of Health and Human Services (DHHS)
Subjects: Sequence Variants, Male, medicine.medical_specialty, Skin Neoplasms, Genotype, Medizin, Identifies 3, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Malignant-melanoma, 0302 clinical medicine, Genetics, medicine, Genetic predisposition, Nevus, Humans, Hla Class-i, Genetic Predisposition to Disease, Polymorphism, Melanoma, 030304 developmental biology, Telomere Length, Cancer, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Loci, Pigmentation, E-cadherin, Single Nucleotide, medicine.disease, Genetic architecture, Attributable Fraction, 3. Good health, Phenotype, Female, Genetic Loci, Genome-Wide Association Study, Cutaneous melanoma, Medical genetics, Settore MED/35 - MALATTIE CUTANEE E VENEREE, 030217 neurology & neurosurgery, Familial Melanoma
Abstract: Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 x 10(-8)) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
Published: 2020

23. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers

Author: Mavaddat, N., Antoniou, A.C., Mooij, T.M., Hooning, M.J., Heemskerk-Gerritsen, B.A., Nogues, C., Laborde, L., Breysse, E., Stoppa-Lyonnet, D., Gauthier-Villars, M., Buecher, B., Caron, O., Fourme-Mouret, E., Fricker, J.P., Lasset, C., Bonadona, V., Berthet, P., Faivre, L., Luporsi, E., Mari, V., Gladieff, L., Gesta, P., Sobol, H., Eisinger, F., Longy, M., Dugast, C., Colas, C., Coupier, I., Pujol, P., Corsini, C., Lortholary, A., Vennin, P., Adenis, C., Nguyen, T.D., Delnatte, C., Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Bignon, Y.J., Demange, L., Penet, C., Dreyfus, H., Cohen-Haguenauer, O., Venat-Bouvet, L., Leroux, D., Zattara-Cannoni, H., Fert-Ferrer, S., Bera, O., Ellis, S., Barrowdale, D., Frost, D., Evans, D.G., Izatt, L., Adlard, J., Eeles, R., Brewer, C., Tischkowitz, M., Henderson, A., Cook, J., Eccles, D., Hogervorst, F.B.L., Collee, J.M., Asperen, C.J. van, Mensenkamp, A.R., Ausems, M.G.E.M., Meijers-Heijboer, H.E.J., Engelen, K. van, Blok, M.J., Oosterwijk, J.C., Verloop, J., Broek, E. van den, Mourits, M.J.E., Koppert, L.B., Hopper, J.L., John, E.M., Chung, W.K., Andrulis, I.L., Daly, M.B., Buys, S.S., Benitez, J., Caldes, T., Jakubowska, A., Simard, J., Singer, C.F., Tan, Y., Olah, E., Navratilova, M., Foretova, L., Gerdes, A.M., Roos-Blom, M.J., Leeuwen, F.E. van, Arver, B., Olsson, H., Schmutzler, R.K., Engel, C., Kast, K., Phillips, K.A., Terry, M.B., Milne, R.L., Goldgar, D.E., Rookus, M.A., Andrieu, N., Easton, D.F., GENEPSO, EMBRACE, HEBON, kConFab Investigators, IBCCS, kConFab, BCFR, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Erasmus MC Cancer Institute, Rotterdam, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Catherine-de-Sienne [Nantes] (CCS), Manchester University NHS Foundation Trust (MFT), Guy's & St Thomas' NHS Foundation Trust, Chapel Allerton Hospital, University of Leeds, Royal Marsden NHS Foundation Trust, Royal Devon & Exeter Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Wessex clinical genetics service, Vrije Universiteit Amsterdam [Amsterdam] (VU), University Medical Center Groningen [Groningen] (UMCG), Department of Medical Genetics, University Medical Center [Utrecht], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Department of Epidemiology, Cancer Prevention Institute of California, Columbia University [New York], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Division of Population Science, Fox Chase Cancer Center, Department of Internal Medicine, Huntsman Cancer Institute, Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Medizinische Universität Wien = Medical University of Vienna, National Institute of Oncology, Masaryk Memorial Cancer Institute (MMCI), Masaryk University [Brno] (MUNI), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, The Netherlands Cancer Institute [Amsterdam, The Netherlands], Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Cancer Epidemiology Centre, Cancer Council Victoria, International Agency for Cancer Research (IACR), Netherlands Cancer Institute, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Andrieu, Nadine, Human genetics, Epidemiology and Data Science, Mavaddat, Nasim [0000-0003-0307-055X], Eeles, Ros [0000-0002-3698-6241], Engel, Christoph [0000-0002-7247-282X], Apollo - University of Cambridge Repository, Pomeranian Medical University-International Hereditary Cancer Centre, Masaryk Memorial Cancer Institute (RECAMO), Columbia Mailman School of Public Health-Columbia University [New York], Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Antoniou, Antonis [0000-0001-9223-3116], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Medical Oncology, Surgery, Cancer Research UK (Reino Unido), NIH - National Cancer Institute (NCI) (Estados Unidos), United States Department of Health and Human Services, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea. European Research Council (ERC), Norwegian EEA Financial Mechanism, Hungarian Scientific Research Fund (Hungría), Ministry of Education, Youth and Sports (República Checa), MH CZ -DRO (MMCI), National Health and Medical Research Council (Australia), Australian National Breast Cancer Foundation, Cancer Australia, ERA-NET TRANSAN JTC 2012 Cancer, Transcan grant, Biotechnology and Biological Sciences Research Council (Reino Unido), Pink Ribbons Project, Netherlands Organisation of Scientific Research, Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Deutsche Krebshilfe, National Institute for Health Research (Reino Unido), Unión Europea. Comisión Europea. 7 Programa Marco, Ministry of Economic Development, Innovation and Export Trade-grant, Canadian Institutes of Health Research, Cancer Research UK, NIH National Cancer Institute (NCI), United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Ministerio de Economia y Competividad (MINECO), European Research Council (ERC), Hungarian Research Grants, MEYS -NPS I, National Health and Medical Research Council of Australia, BBMRI grant, Pink Ribbon grants, Netherlands Organisation of Scientific Research grant, KWF Kankerbestrijding, Instituto de Salud Carlos III - ISCIII, National Institute for Health Research (NIHR), European Union Seventh Framework Program (2007-2013), Canadian Institutes of Health Research (CIHR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), United States of Department of Health & Human Services, European Research Council, APH - Quality of Care, APH - Methodology, Graduate School, ARD - Amsterdam Reproduction and Development, RS: GROW - R4 - Reproductive and Perinatal Medicine, and MUMC+: DA KG Lab Centraal Lab (9)
Subjects: endocrine system diseases, SURGERY, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Cohort Studies, 0302 clinical medicine, BRCA2 Mutation, Breast cancer, Surgical oncology, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Salpingo-oophorectomy/methods, 0303 health sciences, Natural menopause, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Obstetrics, BRCA1 Protein, Breast Neoplasms/epidemiology, Incidence (epidemiology), Incidence, WOMEN, ASSOCIATION, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, OVARIAN, BRCA2 Protein/genetics, 3. Good health, Menopause, Risk-reducing salpingo-oophorectomy, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SURVIVAL, Female, Research Article, Cohort study, Adult, medicine.medical_specialty, Salpingo-oophorectomy, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, lcsh:RC254-282, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, METAANALYSIS, 030304 developmental biology, BRCA2 Protein, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, CONSORTIUM, risk-reducing salpingo-oophorectomy, International Agencies, medicine.disease, BRCA1, BRCA2, KCONFAB, REDUCTION, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, LINK, Mutation, BRCA1 Protein/genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Risk Reduction Behavior
Abstract: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare Diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. INHERIT was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program-grant #CRN-87521-and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie, de la Science et de l' Innovation du Quebec through Genome Quebec, and The Quebec Breast Cancer Foundation. Jacques Simard is a Chairholder of the Canada Research Chair in Oncogenetics. EMBRACE is supported by the Cancer Research UK grants C1287/A23382 and C1287/A16563. D. Gareth Evans is supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by the Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/A11174. MT is funded by the European Union Seventh Framework Program (2007-2013)/European Research Council (310018). The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 110837, Rita K. Schmutzler). The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, no. 2014-008). HCSC was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12-054. The IHCC was supported by Grant PBZ_ KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/2014). This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the National Institute of Health U.S.A. (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation fellow. MODSQUAD-Czech Republic, Brno, was supported by MH CZ -DRO (MMCI, 00209805) and by MEYS -NPS I -LO1413 to LF and MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228, and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Sí
Published: 2020

24. Commentary: Special Report: The Biology of Inequalities in Health: The Lifepath Consortium

Author: Paolo Vineis, Mauricio Avendano-Pabon, Henrique Barros, Mel Bartley, Cristian Carmeli, Luca Carra, Marc Chadeau-Hyam, Giuseppe Costa, Cyrille Delpierre, Angelo D'Errico, Silvia Fraga, Graham Giles, Marcel Goldberg, Michelle Kelly-Irving, Mika Kivimaki, Benoit Lepage, Thierry Lang, Richard Layte, Frances MacGuire, Johan P. Mackenbach, Michael Marmot, Cathal McCrory, Roger L. Milne, Peter Muennig, Wilma Nusselder, Dusan Petrovic, Silvia Polidoro, Fulvio Ricceri, Oliver Robinson, Silvia Stringhini, Marie Zins, Imperial College London, King‘s College London, Epidemiology Research Unit [Porto, Portugal] (EPIUnit), Instituto de Saúde Pública [Porto, Portugal], Universidade do Porto = University of Porto-Universidade do Porto = University of Porto, University College of London [London] (UCL), Université de Lausanne = University of Lausanne (UNIL), Università degli studi di Torino = University of Turin (UNITO), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Piedmont Centre for Drug Addiction Epidemiology, ASLTO3, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, University of Melbourne, Monash University [Melbourne], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Trinity College Dublin, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University [New York], Italian Institute for Genomic Medicine, Geneva University Hospital (HUG), Horizon 2020 grant number 633666- Swiss State Secretariat for Education, Research and Innovation SERI, European Project: 633666,H2020,H2020-PHC-2014-two-stage,LIFEPATH(2015), Commission of the European Communities, Medical Research Council (MRC), Instituto de Saúde Pública da Universidade do Porto, and Public Health
Subjects: [SDV]Life Sciences [q-bio], Psychological intervention, DETERMINANTS, 0302 clinical medicine, Policy and Practice Reviews, 030212 general & internal medicine, Longitudinal Studies, Social science, Child, MESH: Omics, media_common, Public, Environmental & Occupational Health, Executive summary, General Commentary, biology, 030503 health policy & services, lcsh:Public aspects of medicine, MESH: Healthy ageing, socioeconomic position, ASSOCIATION, Causality, Allostatic load, omics, MESH: Socioeconomic position, Europe, healthy aging, social determinants of health, philosophy of science, lifepath consortium, Life course approach, Public Health, 0305 other medical science, Life Sciences & Biomedicine, Adult, causality, Inequality, life-course, media_common.quotation_subject, MESH: Life-course, 1117 Public Health and Health Services, CONDITIONAL CASH TRANSFERS, social inequalities, 03 medical and health sciences, AGE, Environmental health, MESH: Biology, Humans, Social inequality, Social determinants of health, ALLOSTATIC LOAD, Socioeconomic status, Disadvantage, Sedentary lifestyle, ddc:613, ADVERSE CHILDHOOD EXPERIENCES, Philosophy of science, Science & Technology, Australia, Public Health, Environmental and Occupational Health, CAUSE-SPECIFIC MORTALITY, lcsh:RA1-1270, Health Status Disparities, health inequalities, Socioeconomic Factors, MESH: Social inequalities, RISK-FACTORS, OCCUPATIONAL CLASS
Abstract: Funded by the European Commission Horizon 2020 programme, the Lifepath research consortium aimed to investigate the effects of socioeconomic inequalities on the biology of healthy aging. The main research questions included the impact of inequalities on health, the role of behavioral and other risk factors, the underlying biological mechanisms, the efficacy of selected policies, and the general implications of our findings for theories and policies. The project adopted a life-course and comparative approach, considering lifetime effects from childhood and adulthood, and pooled data on up to 1.7 million participants of longitudinal cohort studies from Europe, USA, and Australia. These data showed that socioeconomic circumstances predicted mortality and functional decline as strongly as established risk factors currently targeted by global prevention programmes. Analyses also looked at socioeconomically patterned biological markers, allostatic load, and DNA methylation using richly phenotyped cohorts, unraveling their association with aging processes across the life-course. Lifepath studies suggest that socioeconomic circumstances are embedded in our biology from the outset—i.e., disadvantage influences biological systems from molecules to organs. Our findings have important implications for policy, suggesting that (a) intervening on unfavorable socioeconomic conditions is complementary and as important as targeting well-known risk factors, such as tobacco and alcohol consumption, low fruit and vegetable intake, obesity and a sedentary lifestyle, and that (b) effects of preventive interventions in early life integrate interventions in adulthood. The report has an executive summary that refers to the different sections of the main paper. This study was supported by the European Commission (Horizon 2020 grant number 633666) and the Swiss State Secretariat for Education, Research and Innovation SERI.
Published: 2020

25. Alcohol consumption, cigarette smoking, and risk of breast cancer for BRCA1 and BRCA2 mutation carriers: results from The BRCA1 and BRCA2 Cohort Consortium

Author: Terry, Mary Beth, Noguès, Catherine, Barrowdale, Daniel, Frost, Debra, Brewer, Carole, Evans, D. Gareth, Izatt, Louise, Side, Lucy, Walker, Lisa, Tischkowitz, Marc, Rogers, Mark, Porteous, Mary, Meijers-Heijboer, Hanne E.J., Gille, Johan JP, Blok, Marinus, Hoogerbrugge, Nicoline, Daly, Mary, Andrulis, Irene, Buys, Saundra, John, Esther, McLachlan, Sue-Anne, Friedlander, Michael, Tan, Yen, Osorio, Ana, Caldés, Trinidad, Jakubowska, Anna, Simard, Jacques, Singer, Christian, Olah, Edith, Navratilova, Marie, Foretova, Lenka, Gerdes, Anne-Marie, Roos-Blom, Marie-José, Arver, Brita, Olsson, Håkan, Schmutzler, Rita, Hopper, John, Milne, Roger, Easton, Douglas, Van Leeuwen, Flora, Rookus, Matti, Andrieu, Nadine, Goldgar, David, Huntsman Cancer Institute [Salt Lake City], University of Utah, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Department of Clinical Genetics, Royal Devon & Exeter Hospital, Genetic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre, University of Manchester, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Department of Clinical Genetics, The Churchill, Oxford, Oxford Regional Genetics Service [Oxford, UK], Churchill Hospital Oxford Centre for Haematology, Department of Genetics, Portuguese Oncology Institute, Department of Computer Science [Colorado State University], Colorado State University [Fort Collins] (CSU), West General Hospital, VU University Medical Center [Amsterdam], University Hospital Maastricht, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Division of Population Science, Fox Chase Cancer Center, Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Internal Medicine, Huntsman Cancer Institute, Department of Epidemiology, Cancer Prevention Institute of California, St. Vincent's Hospital, Sydney, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Medical University of Vienna, Human Genetics Group, Spanish National Cancer Research Centre, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Laboratoire de Génomique des Cancers, Laval University [Québec], Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, National Institute of Oncology, Masaryk Memorial Cancer Institute (RECAMO), Odense University Hospital, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Cancer Genetic Epidemiology [Cambridge], Department of Oncology-University of Cambridge [UK] (CAM), Departments of Epidemiology and Molecular Pathology, The Netherlands Cancer Institute, Netherlands Cancer Institute, Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre national d'études agronomiques des régions chaudes (CNEARC)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Department of Dermatology [Salt Lake City, UT, USA], University of Utah School of Medicine [Salt Lake City], This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195, 1100868), the Australian National Breast Cancer Foundation (IF 17), the National Health and Medical Research Council (454508, 288704, 145684), the National Institute of Health U.S.A. (1RO1CA159868), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Kelly Phillips is an Australian National Breast Cancer Foundation fellow.Lenka Foretova was supported by MH CZ - DRO (MMCI, 00209805) and by MEYS - NPS I- LO1413 to LF, MN. Edith Olah and The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/ÖP-9. Hakan Olsson and Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society., Medizinische Universität Wien = Medical University of Vienna, Université Laval [Québec] (ULaval), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], MINES ParisTech - École nationale supérieure des mines de Paris, and Université Paris sciences et lettres (PSL)
Subjects: breast cancer, endocrine system diseases, alcohol, cigarette smoking, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, skin and connective tissue diseases, BRCA1, BRCA2
Abstract: International audience; BACKGROUND:Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer (BC), but very few studies have examined these effects in BRCA1 and BRCA2 mutation carriers. Given the high BC risk for mutation carriers and the importance of BRCA1 and BRCA2 in DNA repair, better evidence on the associations of these lifestyle factors with BC risk is essential.METHODS:Using a large international pooled cohort of BRCA1 and BRCA2 mutation carriers, we conducted retrospective (5,707 BRCA1 mutation carriers; 3,525 BRCA2 mutation carriers) and prospective (2,276 BRCA1 mutation carriers; 1,610 BRCA2 mutation carriers) analyses of alcohol and tobacco consumption using Cox proportional hazards models.RESULTS:For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with BC risk, except smoking for more than five years before a first full-term pregnancy (FFTP) when compared to parous women who never smoked. For BRCA1 mutation carriers, the HR from retrospective analysis (HRR) was 1.19 (95%CI:1.02,1.39) and the HR from prospective analysis (HRP) was 1.36 (95%CI:0.99,1.87). For BRCA2 mutation carriers, smoking for more than five years before a FFTP showed an association of a similar magnitude, but the confidence limits were wider (HRR=1.25,95%CI:1.01,1.55 and HRP=1.30,95%CI:0.83,2.01). For both carrier groups, alcohol consumption was not associated with BC risk.CONCLUSIONS:The finding that smoking during the pre-reproductive years increases BC risk for mutation carriers warrants further investigation.IMPACT:This is the largest prospective study of BRCA mutation carriers to assess these important risk factors.
Published: 2019

26. Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Author: Paul Brennan, M. G. Ennas, Qing Lan, Sasha Bernatsky, Alan A. Arslan, Peter Kraft, Lohith Madireddy, Roel Vermeulen, Kenan Onel, Graham G. Giles, John J. Spinelli, Eleanor Kane, Bengt Glimelius, Alexandra Nieters, David V. Conti, Christine F. Skibola, Pouya Khankhanian, Amy Moore, Ruth C. Travis, Mads Melbye, Sonja I. Berndt, Mark Liebow, Lauren R. Teras, Pierluigi Cocco, Lennox Din, Alain Monnereau, Mark P. Purdue, Lenka Foretova, Stephen J. Chanock, Stephen M. Ansell, Angela Brooks-Wilson, Wendy Cozen, Kenneth Offit, Demetrius Albanes, Anne J. Novak, Melissa C. Southey, Paolo Boffetta, Nicola J. Camp, James R. Cerhan, Rudolph Kaaks, Silvia de Sanjosé, Karen Curtin, Sophia S. Wang, James McKay, Nicole Wong Doo, Hans-Olov Adami, Tongzhang Zheng, Claire M. Vajdic, Nisha Pradhan, Giacomo Muzi, Gilles Salles, Nathaniel Rothman, Yolanda Benavente, Marc Maynadié, Brian K. Link, Delphine Casabonne, Hervé Ghesquières, Joseph Vijai, Karin E. Smedby, Paige M. Bracci, David G. Cox, Brenda M. Birmann, Lucia Miligi, Carolyn Stewart, Lucia Conde, Leonid Padyukov, Eve Roman, Richard K. Severson, Jorge R. Oksenberg, Immaculata De Vivo, Yawei Zhang, Corrado Magnani, Jacqueline Clavel, Lindsay M. Morton, Corinne Haioun, Jonathan N. Hofmann, Karen H. Costenbader, Pierre-Antoine Gourraud, Mohammad Sheikh, Stephanie J. Weinstein, Susan L. Slager, Paolo Vineis, Nikitha Kosaraju, Zachary Taub, Henrik Hjalgrim, Roger L. Milne, Morris Din, Martha Glenn, Nikolaus Becker, Timothy J. Vyse, Thomas M. Mack, Anthony Staines, Department of Medicine, Clinical Epidemiology, McGill University Health Center [Montreal] (MUHC), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Emory University [Atlanta, GA], Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, International Agency for Cancer Research (IACR), Department of Public Health, Vientiane Municipality, Registre des hémopathies malignes de Côte d'Or, Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, GRAPHOS - IFROSS Recherche, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Faculty of Medicine, Section of Rheumatology, Imperial College London, Karolinska Institutet [Stockholm], Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Uppsala Universitet [Uppsala], Carver College of Medicine, University of Iowa, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Cancer Epidemiology and Genetics, National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Health Sciences, University of York [York, UK], Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), University of Melbourne, Centre Léon Bérard [Lyon], Mayo Clinic [Rochester], Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), Memorial Sloane Kettering Cancer Center [New York], Huntsman Cancer Institute, Clinical Genetics Service, ISPO - Cancer Prevention and Research Institute, Unit of Environmental and Occupational Epidemiology, Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], B.B. Brodie Department of Neuroscience, Department of Pathology, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Unit of Environment Cancer Epidemiology, IARC, University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), Department of Epidemiology, Harvard School of Public Health, Wayne State University [Detroit], Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Cancer Epidemiology Centre, Cancer Council Victoria, Cancer Epidemiology Unit, University of Oxford [Oxford], De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (MONARIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Catalan Institute of Oncology (ICO), Department of Neurology [San Francisco, CA, USA], University of California [San Francisco] (UCSF), University of California-University of California, Norris Comprehensive Cancer Center, Masaryk University [Brno] (MUNI), Università degli studi di Torino = University of Turin (UNITO), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Imperial College London, University of Oxford, Din L., Sheikh M., Kosaraju N., Smedby K.E., Bernatsky S., Berndt S.I., Skibola C.F., Nieters A., Wang S., McKay J.D., Cocco P., Maynadie M., Foretova L., Staines A., Mack T.M., de Sanjose S., Vyse T.J., Padyukov L., Monnereau A., Arslan A.A., Moore A., Brooks-Wilson A.R., Novak A.J., Glimelius B., Birmann B.M., Link B.K., Stewart C., Vajdic C.M., Haioun C., Magnani C., Conti D.V., Cox D.G., Casabonne D., Albanes D., Kane E., Roman E., Muzi G., Salles G., Giles G.G., Adami H.-O., Ghesquieres H., De Vivo I., Clavel J., Cerhan J.R., Spinelli J.J., Hofmann J., Vijai J., Curtin K., Costenbader K.H., Onel K., Offit K., Teras L.R., Morton L., Conde L., Miligi L., Melbye M., Ennas M.G., Liebow M., Purdue M.P., Glenn M., Southey M.C., Din M., Rothman N., Camp N.J., Wong Doo N., Becker N., Pradhan N., Bracci P.M., Boffetta P., Vineis P., Brennan P., Kraft P., Lan Q., Severson R.K., Vermeulen R.C.H., Milne R.L., Kaaks R., Travis R.C., Weinstein S.J., Chanock S.J., Ansell S.M., Slager S.L., Zheng T., Zhang Y., Benavente Y., Taub Z., Madireddy L., Gourraud P.-A., Oksenberg J.R., Cozen W., Hjalgrim H., Khankhanian P., and Le Bihan, Sylvie
Subjects: Oncology, Male, Multifactorial Inheritance, Lymphoma, Epidemiology, Chronic lymphocytic leukemia, Follicular lymphoma, Genome-wide association study, Disease, Neurodegenerative, meta-analysi, immune system diseases, HLA Antigens, Risk Factors, hemic and lymphatic diseases, 2.1 Biological and endogenous factors, HLA Antigen, Aetiology, Genetics (clinical), Cancer, Allele, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Lymphoma, Non-Hodgkin, non-Hodgkin lymphoma, 030305 genetics & heredity, Single Nucleotide, Hematology, Middle Aged, 3. Good health, Public Health and Health Services, Female, Human, medicine.medical_specialty, autoimmune disease, genome-wide association study, meta-analysis, Alleles, Autoimmune Diseases, Humans, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Non-Hodgkin, Article, 03 medical and health sciences, Rare Diseases, Internal medicine, Genetic variation, medicine, Genetics, Polymorphism, 030304 developmental biology, Autoimmune disease, business.industry, Multiple sclerosis, Risk Factor, Arthritis, Inflammatory and immune system, Human Genome, medicine.disease, Brain Disorders, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
Published: 2019

27. Plain packaging: legislative differences in Australia, France, the UK, New Zealand and Norway, and options for strengthening regulations

Author: Kylie Lindorff, Janne Scheffels, Crawford Moodie, Janet Hoek, Karine Gallopel-Morvan, University of Stirling, University of Otago [Dunedin, Nouvelle-Zélande], Norwegian Institute of Public Health [Oslo] (NIPH), École des Hautes Études en Santé Publique [EHESP] (EHESP), EA Management des Organisations de Santé (EA MOS), École des Hautes Études en Santé Publique [EHESP] (EHESP)-PRES Sorbonne Paris Cité, Institut du Management (IDM), and Cancer Epidemiology Centre, Cancer Council Victoria
Subjects: Health (social science), Time Factors, Public policy, Best practice, Global health, Legislation, Product Labeling, Terminology, 03 medical and health sciences, 0302 clinical medicine, Terminology as Topic, Milestone (project management), Product Packaging, Humans, 030212 general & internal medicine, Marketing, Government, 030505 public health, Public Health, Environmental and Occupational Health, Legislature, Tobacco Products, Quitline, Packaging, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, 0305 other medical science
Abstract: International audience; By July 2018, five countries (Australia, France, the UK, New Zealand and Norway) had fully implemented plain (standardised) packaging. Using government documents, we reviewed the key legislative differences between these five countries to identify best practice measures and potential lacuna. We then discuss how governments planning to introduce plain packaging could strengthen their legislation. Differences between countries include the terminology used (either ‘plain’, ‘standardised’ or ‘plain and standardised’), products covered and transition times (ranging from 2 to 12 months). Myriad differences exist with respect to the packaging, including the dimensions (explicitly stated for height, width and depth vs minimum dimensions for the health warnings only), structure (straight-edged flip-top packs vs straight, rounded and bevelled-edged flip-top packs and shoulder boxes) and size (minimum number of cigarettes and weight of tobacco vs fixed amounts) and warning content (eg, inclusion of a stop-smoking web address and/or quitline displayed on warnings on one or both principal display areas). Future options that merit further analysis include banning colour descriptors in brand and variant names, allowing pack inserts promoting cessation and permitting cigarettes that are designed to be dissuasive. Plain packaging legislation and regulations are divergent. Countries moving towards plain packaging should consider incorporating the strengths of existing policies and review opportunities for extending these. While plain packaging represents a milestone in tobacco-control policy, future legislation need not simply reflect the past but could set new benchmarks to maximise the potential benefits of this policy.
Published: 2019

28. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk

Author: Cyrille Cuenin, Salvatore Panico, Rosario Tumino, Anthony J. Swerdlow, Domenico Palli, Pierre Antoine Dugué, Nick Orr, Sara Grioni, Michael Jones, Francesca Fasanelli, Isabelle Romieu, Silvia Polidoro, Vittorio Perduca, Srikant Ambatipudi, Melissa C. Southey, Minouk J. Schoemaker, Olivia Fletcher, Graham G. Giles, Paolo Vineis, Maria Concetta Giurdanella, Giovanna Masala, James M. Flanagan, Annelie Johansson, Amalia Mattiello, Nichola Johnson, Dallas R. English, Gianluca Severi, Katarzyna Tomczyk, Roger L. Milne, Carlotta Sacerdote, Claudia Agnoli, Laura Baglietto, Veronique Chajes, Zdenko Herceg, Breast Cancer Now, Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Epidemiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Cancer Registry, Center for Cancer Prevention, CPO-Piemonte, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Human Genetics Foundation (HuGeF), Torino, Italy., The institute of cancer research [London], Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia, parent, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne, Cancer Epidemiology Centre, Cancer Council Victoria, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), International Agency for Cancer Research (IACR), Epidemiology section, Institute of Cancer Research in Sutton, University of Torino and CPO-Piemonte, Università degli studi di Torino (UNITO), Perduca, Vittorio, University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli studi di Torino = University of Turin (UNITO)
Subjects: BIOMARKER, 0301 basic medicine, Oncology, Bisulfite sequencing, Epigenesis, Genetic, Cancer risk, REANALYSIS, Breast cancer, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], Prospective Studies, skin and connective tissue diseases, Prospective cohort study, Genetics (clinical), Genetics & Heredity, [STAT.AP]Statistics [stat]/Applications [stat.AP], OUTCOMES, DNA methylation, WOMEN, Middle Aged, Biomarker, Epigenetics, Estrogen exposure, EWAS, Hormonal exposures, 3. Good health, Italy, CpG site, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, PERIPHERAL-BLOOD, 03 medical and health sciences, AGE, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Molecular Biology, METAANALYSIS, Science & Technology, business.industry, Research, Case-control study, Cancer, Estrogens, medicine.disease, BODY-MASS INDEX, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, CpG Islands, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SEX-HORMONES, business, Genome-Wide Association Study, Developmental Biology
Abstract: Background It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman’s total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. Methods An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. Results We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04–1.07, P = 3 × 10−12) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q
Published: 2019

29. A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk

Author: Bernd Holleczek, Demetrius Albanes, Stephanie J. Weinstein, Yuen Y. E. Wong, Michael B. Cook, Alison M. Mondul, Konstantinos K. Tsilidis, Christopher A. Haiman, Jeannette M. Schenk, Kala Visvanathan, Loic Le Marchand, María José Sánchez, Pamela L. Lutsey, Freddie C. Hamdy, Harri Rissanen, Jenny L Donovan, Marc J. Gunter, David E. Neal, Shoichiro Tsugane, Bas Bueno-de-Mesquita, Tone Bjørge, Haakon E. Meyer, Rune Blomhoff, Mélanie Deschasaux, Mathilde Touvier, Pilar Galan, Lynne R. Wilkens, Tracy M. Layne, Johan Malm, Serge Hercberg, Timothy J. Key, Antonia Trichopoulou, Petra H.M. Peeters, Randi Elin Gislefoss, Amanda Black, Ruth C. Travis, Osvaldo P. Almeida, Domenico Palli, June M. Chan, Martin Almquist, Darryl W. Eyles, Elizabeth A. Williamson, Anja Olsen, Kathy J. Helzlsouer, Paul N. Appleby, Jonas Manjer, Hermann Brenner, Wen Yi Huang, Edward Giovannucci, Corinne E. Joshu, Regina G. Ziegler, Leon Flicker, Naomi E. Allen, Bu B. Yeap, Laura Perna, Giske Ursin, Meir J. Stampfer, Catherine M. Tangen, Richard M. Martin, Aurora Perez-Cornago, Norie Sawada, Paul Knekt, Ben Schöttker, Elizabeth A. Platz, Alicia K Heath, Dallas R. English, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Division of Epidemiology and Community Health, University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Michigan [Ann Arbor], University of Michigan System, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Hellenic Health Foundation, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Epidemiology and Biostatistics [Imperial College London], Imperial College London, Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Saarland Cancer Registry, National Institute for Health and Welfare [Helsinki], The University of Western Australia (UWA), University of California [San Francisco] (UCSF), University of California, Harvard T.H. Chan School of Public Health, Cancer Registry of Norway, Institute of Population-based Cancer Research, University of Oslo (UiO), National Cancer Center, Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Queensland Brain Institute, University of Queensland [Brisbane], London School of Hygiene and Tropical Medicine (LSHTM), Skane University Hospital [Lund], University of Hawai'i [Honolulu] (UH), Keck School of Medicine [Los Angeles], University of Southern California (USC), Cancer Prevention Program, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), SWOG Southwest Oncology Group, University of Bristol [Bristol], Nuffield Department of Surgery, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota [Twin Cities] (UMN), Melbourne School for Population and Global Health-University of Melbourne, Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Cancer Research UK [C8221/A19170]
Subjects: Male, 0301 basic medicine, Oncology, 1,25-dihydroxyvitamin D, Aging, Cancer Research, MESH: Risk Assessment/methods, MESH: Prostatic Neoplasms/etiology, Disease, Prostate cancer, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Odds Ratio, Prospective Studies, Vitamin D, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Cancer, MESH: Aged, MESH: Middle Aged, Prostate Cancer, Middle Aged, 25-hydroxyvitamin D, MESH: Case-Control Studies, 3. Good health, d metabolites, Centre for Surgical Research, 030220 oncology & carcinogenesis, ICEP, pooled analysis, Risk assessment, Life Sciences & Biomedicine, Urologic Diseases, medicine.medical_specialty, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Article, vitamin D deficiency, 03 medical and health sciences, MESH: Cross-Sectional Studies, serum 25-hydroxyvitamin d, Clinical Research, subsequent development, Internal medicine, 1,25-DIHYDROXYVITAMIN-D, medicine, Vitamin D and neurology, Journal Article, Humans, Oncology & Carcinogenesis, MESH: Vitamin D/blood, Aged, Nutrition, Science & Technology, MESH: Humans, business.industry, Prevention, Case-control study, Prostatic Neoplasms, Odds ratio, medicine.disease, MESH: Male, MESH: Odds Ratio, MESH: Prospective Studies, Cross-Sectional Studies, 030104 developmental biology, 1,25-dihydroxivatmin-d, Case-Control Studies, MESH: Vitamin D/analogs & derivatives, MESH: Prostatic Neoplasms/blood, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, polymorphisms, 1112 Oncology And Carcinogenesis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13–1.31; P trend < 0.001). However, this association varied by disease aggressiveness (Pheterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13–1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78–1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. Significance: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.
Published: 2019

30. Development and performance evaluation of a GIS-based metric to assess exposure to airborne pollutant emissions from industrial sources

Author: Elodie Faure, Thomas Coudon, Francesca Mancini, Pietro Salizzoni, Aurélie M N Danjou, Gianluca Severi, Delphine Praud, Béatrice Fervers, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Cancer Epidemiology Centre, Cancer Council Victoria, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Coefficient of determination, Geographic information system, Health, Toxicology and Mutagenesis, Breast Neoplasms, 010501 environmental sciences, Dioxins, 01 natural sciences, Dispersion modelling, lcsh:RC963-969, 03 medical and health sciences, 0302 clinical medicine, Cohen's kappa, Air Pollution, Statistics, Humans, Industry, Statistical dispersion, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Cancer, 0105 earth and related environmental sciences, Exposure assessment, Air Pollutants, SIRANE, [SDE.IE]Environmental Sciences/Environmental Engineering, business.industry, lcsh:Public aspects of medicine, Methodology, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Atmospheric dispersion modeling, GIS, Emission intensity, 13. Climate action, Case-Control Studies, Geographic Information Systems, lcsh:Industrial medicine. Industrial hygiene, Environmental science, Female, France, Metric (unit), business, Environmental Monitoring, Cadmium
Abstract: Background Dioxins are environmental and persistent organic carcinogens with endocrine disrupting properties. A positive association with several cancers, including risk of breast cancer has been suggested. Objectives This study aimed to develop and assess performances of an exposure metric based on a Geographic Information System (GIS) through comparison with a validated dispersion model to estimate historical industrial dioxin exposure for its use in a case-control study nested within a prospective cohort. Methods Industrial dioxin sources were inventoried over the whole French territory (n > 2500) and annual average releases were estimated between 1990 and 2008. In three selected areas (rural, urban and urban-costal), dioxin dispersion was modelled using SIRANE, an urban Gaussian model and exposure of the French E3N cohort participants was estimated. The GIS-based metric was developed, calibrated and compared to SIRANE results using a set of parameters (local meteorological data, characteristics of industrial sources, e.g. emission intensity and stack height), by calculating weighted kappa statistics (wκ) and coefficient of determination (R2). Furthermore, as performance evaluation, the final GIS-based metric was tested to assess atmospheric exposure to cadmium. Results The concordance between the GIS-based metric and the dispersion model for dioxin exposure estimate was strong (wκ median = 0.78 (1st quintile = 0.72, 3rd quintile =0.82) and R2 median = 0.82 (1st quintile = 0.71, 3rd quintile = 0.87)). We observed similar performance for cadmium. Conclusions Our study demonstrated the ability of the GIS-based metric to reliably characterize long-term environmental dioxin and cadmium exposures as well as the pertinence of using dispersion modelling to construct and calibrate the GIS-based metric. Electronic supplementary material The online version of this article (10.1186/s12940-019-0446-x) contains supplementary material, which is available to authorized users.
Published: 2019

31. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Author: Figlioli, G., Bogliolo, M., Catucci, I., Caleca, L., Lasheras, S. V., Pujol, R., Kiiski, J. I., Muranen, T. A., Barnes, D. R., Dennis, J., Michailidou, K., Bolla, M. K., Leslie, G., Aalfs, C. M., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C. S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Adank, M. A., Adlard, J., Agata, S., Cadoo, K., Agnarsson, B. A., Ahearn, T., Aittomaki, K., Ambrosone, C. B., Andrews, L., Anton-Culver, H., Antonenkova, N. N., Arndt, V., Arnold, N., Aronson, K. J., Arun, B. K., Asseryanis, E., Auber, B., Auvinen, P., Azzollini, J., Balmana, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., Beane Freeman, L. E., Beauparlant, C. J., Beckmann, M. W., Behrens, S., Benitez, J., Berger, R., Bermisheva, M., Blanco, A. M., Blomqvist, C., Bogdanova, N. V., Bojesen, A., Bojesen, S. E., Bonanni, B., Borg, A., Brady, A. F., Brauch, H., Brenner, H., Bruning, T., Burwinkel, B., Buys, S. S., Caldes, T., Caliebe, A., Caligo, M. A., Campa, D., Campbell, I. G., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Claes, K. B. M., Clarke, C. L., Collavoli, A., Conner, T. A., Cox, D. G., Cybulski, C., Czene, K., Daly, M. B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y. C., Dite, G. S., Ditsch, N., Domchek, S. M., Dorfling, C. M., dos-Santos-Silva, I., Durda, K., Dwek, M., Eccles, D. M., Ekici, A. B., Eliassen, A. H., Ellberg, C., Eriksson, M., Evans, D. G., Fasching, P. A., Figueroa, J., Flyger, H., Foulkes, W. D., Friebel, T. M., Friedman, E., Gabrielson, M., Gaddam, P., Gago-Dominguez, M., Gao, C., Gapstur, S. M., Garber, J., Garcia-Closas, M., Garcia-Saenz, J. A., Gaudet, M. M., Gayther, S. A., Belotti, M., Bertrand, O., Birot, A. -M., Buecher, B., Caputo, S., Dupre, A., Fourme, E., Gauthier-Villars, M., Golmard, L., Le Mentec, M., Moncoutier, V., de Pauw, A., Saule, C., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Bressac-de-Paillerets, B., Caron, O., Guillaud-Bataille, M., Bignon, Y. -J., Uhrhammer, N., Bonadona, V., Lasset, C., Berthet, P., Castera, L., Vaur, D., Bourdon, V., Nogues, C., Noguchi, T., Popovici, C., Remenieras, A., Sobol, H., Coupier, I., Pujol, P., Adenis, C., Dumont, A., Revillion, F., Muller, D., Barouk-Simonet, E., Bonnet, F., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Guimbaud, R., Feillel, V., Toulas, C., Dreyfus, H., Leroux, C. D., Peysselon, M., Rebischung, C., Legrand, C., Baurand, A., Bertolone, G., Coron, F., Faivre, L., Jacquot, C., Lizard, S., Kientz, C., Lebrun, M., Prieur, F., Fert-Ferrer, S., Mari, V., Venat-Bouvet, L., Bezieau, S., Delnatte, C., Mortemousque, I., Colas, C., Coulet, F., Soubrier, F., Warcoin, M., Bronner, M., Sokolowska, J., Collonge-Rame, M. -A., Damette, A., Gesta, P., Lallaoui, H., Chiesa, J., Molina-Gomes, D., Ingster, O., Manouvrier-Hanu, S., Lejeune, S., Giles, G. G., Glendon, G., Godwin, A. K., Goldberg, M. S., Goldgar, D. E., Guenel, P., Gutierrez-Barrera, A. M., Haeberle, L., Haiman, C. A., Hakansson, N., Hall, P., Hamann, U., Harrington, P. A., Hein, A., Heyworth, J., Hillemanns, P., Hollestelle, A., Hopper, J. L., Hosgood, H. D., Howell, A., Hu, C., Hulick, P. J., Hunter, D. J., Imyanitov, E. N., Aghmesheh, M., Greening, S., Amor, D., Gattas, M., Botes, L., Buckley, M., Friedlander, M., Koehler, J., Meiser, B., Saleh, M., Salisbury, E., Trainer, A., Tucker, K., Antill, Y., Dobrovic, A., Fellows, A., Fox, S., Harris, M., Nightingale, S., Phillips, K., Sambrook, J., Thorne, H., Armitage, S., Arnold, L., Kefford, R., Kirk, J., Rickard, E., Bastick, P., Beesley, J., Hayward, N., Spurdle, A., Walker, L., Beilby, J., Saunders, C., Bennett, I., Blackburn, A., Bogwitz, M., Gaff, C., Lindeman, G., Pachter, N., Scott, C., Sexton, A., Visvader, J., Taylor, J., Winship, I., Brennan, M., Brown, M., French, J., Edwards, S., Burgess, M., Burke, J., Patterson, B., Butow, P., Culling, B., Caldon, L., Callen, D., Chauhan, D., Eisenbruch, M., Heiniger, L., Chauhan, M., Christian, A., Dixon, J., Kidd, A., Cohen, P., Colley, A., Fenton, G., Crook, A., Dickson, R., Field, M., Cui, J., Cummings, M., Dawson, S. -J., Defazio, A., Delatycki, M., Dudding, T., Edkins, T., Farshid, G., Flanagan, J., Fong, P., Forrest, L., Gallego-Ortega, D., George, P., Gill, G., Kollias, J., Haan, E., Hart, S., Jenkins, M., Hunt, C., Lakhani, S., Lipton, L., Lobb, L., Mann, G., Mclachlan, S. A., O'Connell, S., O'Sullivan, S., Pieper, E., Robinson, B., Saunus, J., Scott, E., Shelling, A., Williams, R., Young, M. A., Isaacs, C., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E. M., Jones, M. E., Jung, A., Kaaks, R., Karlan, B. Y., Khusnutdinova, E., Kitahara, C. M., Konstantopoulou, I., Koutros, S., Kraft, P., Lambrechts, D., Lazaro, C., Le Marchand, L., Lester, J., Lesueur, F., Lilyquist, J., Loud, J. T., K. H., Lu, Luben, R. N., Lubinski, J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martens, J. W. M., Maurer, T., Mavroudis, D., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Montagna, M., Nathanson, K. L., Neuhausen, S. L., Newman, W. G., Nguyen-Dumont, T., Nielsen, F. C., Nielsen, S., Nikitina-Zake, L., Offit, K., Olah, E., Olopade, O. I., Olshan, A. F., Olson, J. E., Olsson, H., Osorio, A., Ottini, L., Peissel, B., Peixoto, A., Peto, J., Plaseska-Karanfilska, D., Pocza, T., Presneau, N., Pujana, M. A., Punie, K., Rack, B., Rantala, J., Rashid, M. U., Rau-Murthy, R., Rennert, G., Lejbkowicz, F., Rhenius, V., Romero, A., Rookus, M. A., Ross, E. A., Rossing, M., Rudaitis, V., Ruebner, M., Saloustros, E., Sanden, K., Santamarina, M., Scheuner, M. T., Schmutzler, R. K., Schneider, M., Senter, L., Shah, M., Sharma, P., Shu, X. -O., Simard, J., Singer, C. F., Sohn, C., Soucy, P., Southey, M. C., Spinelli, J. J., Steele, L., Stoppa-Lyonnet, D., Tapper, W. J., Teixeira, M. R., Terry, M. B., Thomassen, M., Thompson, J., Thull, D. L., Tischkowitz, M., Tollenaar, R. A. E. M., Torres, D., Troester, M. A., Truong, T., Tung, N., Untch, M., Vachon, C. M., van Rensburg, E. J., van Veen, E. M., Vega, A., Viel, A., Wappenschmidt, B., Weitzel, J. N., Wendt, C., Wieme, G., Wolk, A., Yang, X. R., Zheng, W., Ziogas, A., Zorn, K. K., Dunning, A. M., Lush, M., Wang, Q., Mcguffog, L., Parsons, M. T., Pharoah, P. D. P., Fostira, F., Toland, A. E., Andrulis, I. L., Ramus, S. J., Swerdlow, A. J., Greene, M. H., Chung, W. K., Milne, R. L., Chenevix-Trench, G., Dork, T., Schmidt, M. K., Easton, D. F., Radice, P., Hahnen, E., Antoniou, A. C., Couch, F. J., Nevanlinna, H., Surralles, J., Peterlongo, P., Caleca, Laura [0000-0002-3381-7493], Muranen, Taru A. [0000-0002-5895-1808], Dennis, Joe [0000-0003-4591-1214], Adlard, Julian [0000-0002-1693-0435], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Devilee, Peter [0000-0002-8023-2009], Foulkes, William D. [0000-0001-7427-4651], Isaacs, Claudine [0000-0002-9646-1260], Jakimovska, Milena [0000-0002-1506-0669], Konstantopoulou, Irene [0000-0002-0470-0309], Lesueur, Fabienne [0000-0001-7404-4549], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Peto, Julian [0000-0002-1685-8912], Punie, Kevin [0000-0002-1162-7963], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Viel, Alessandra [0000-0003-2804-0840], Wieme, Greet [0000-0003-2718-5300], Zheng, Wei [0000-0003-1226-070X], Ziogas, Argyrios [0000-0003-4529-3727], Greene, Mark H. [0000-0003-1852-9239], Nevanlinna, Heli [0000-0002-0916-2976], Peterlongo, Paolo [0000-0001-6951-6855], Apollo - University of Cambridge Repository, Medical Oncology, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Yorkshire Regional Genetics Service, Department of Pathology, University Hospital and University of Iceland School of Medicine, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], University of Iceland [Reykjavik]-Landspitali - University Hospital, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Leicestershire Clinical Genetics Service, University Hospitals Leicester, Occupational and Environmental Epidemiology Branch [Bethesda, Maryland], Division of Cancer Epidemiology and Genetics [Bethesda, Maryland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Chaim Sheba Medical Center, Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Department of Oncology, Department of Obstetrics and Gynaecology (MHH), Hannover Medical School [Hannover] (MHH), Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, North West Thames Regional Genetics, Northwick Park Hospital, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Division of Clinical Epidemiology and Aging Research, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Molecular Epidemiology Research Group, Department of Internal Medicine, Huntsman Cancer Institute, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Cancer Epidemiology, Division of Cancer Epidemiology, Division of Cancer Epidemiology and Genetics, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Division of Population Science, Fox Chase Cancer Center, Department of Human Genetics & Department of Pathology, Leiden University Medical Center (LUMC), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Obstetrics and Gynecology [Munich, Germany], University-Hospital Munich-Großhadern [München]-Ludwig Maximilian University [Munich] (LMU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Wessex clinical genetics service, Lund University Hospital, Department of Genomic Medicine, University of Manchester [Manchester], Department of Breast Surgery, Herlev and Gentofte Hospital, Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, National Institutes of Health [Bethesda] (NIH), Epidemiology Research Program, American Cancer Society, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Melbourne, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], International Agency for Cancer Research (IACR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of OB/Gyn, University Breast Center Franconia, Univeristy Hospital Erlangen, Molecular Genetics of Breast Cancer, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, The Christie, Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Department of Gynecology and Obstetrics, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Epidemiology, Cancer Prevention Institute of California, Unit of Nutrition and Cancer, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Institute of Biochemistry and Genetics [Bashkortostan Republic, Russia], Russian Academy of Sciences / Ufa Scientific Centre [Bashkortostan Republic, Russia]], National Center for Scientific Research 'Demokritos' (NCSR), Harvard School of Public Health, Laboratory for translational genetics Leuven, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, University of Hawai‘i [Mānoa] (UHM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Genetics Branch, Strangeways Research Laboratory, Unit of Medical Genetics, Fondazione IRCCS INT, Department of Gynaecology and Obstetrics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Women's Health [London], University College London Hospitals (UCLH), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Department of Population Sciences, Beckman Research Institute of City of Hope, Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, University of Chicago, Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Genetics Group, Spanish National Cancer Research Centre, Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Genetics, Portuguese Oncology Institute, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), University of Munich, Karolinska University Hospital [Stockholm], Umm Al-Qura University, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Netherlands Cancer Institute, IT University of Copenhagen (ITU), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Queen's University [Belfast] (QUB), Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University School of Medicine [Nashville], Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Universität Heidelberg [Heidelberg], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Odense University Hospital, Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), HELIOS Hospital Berlin-Buch, Cancer Genetics Laboratory, University of Pretoria [South Africa], Genomic Medicine Group, Universidade de Santiago de Compostela [Spain] (USC ), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of Science and Technology Beijing [Beijing] (USTB), University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Université de Pau et des Pays de l'Adour (UPPA), Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, The institute of cancer research [London], Department of Medical Genetics, Mayo Clinic, Cancer Epidemiology Centre, Cancer Council Victoria, Queensland Institute of Medical Research, Cancer Research U.K. Genetic Epidemiology Unit, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Department of Laboratory Medicine and Pathology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Muranen, Taru A [0000-0002-5895-1808], Foulkes, William D [0000-0001-7427-4651], Greene, Mark H [0000-0003-1852-9239], Institut Català de la Salut, [Figlioli G, Catucci I] IFOM - the FIRC Institute for Molecular Oncology, Genome Diagnostics Program, Milan, Italy. [Bogliolo M, Pujol R] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. Institute of Biomedical Research, Sant Pau Hospital, Barcelona, Spain. [Caleca L] Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy. [Lasheras SV] Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Genètica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Hospital Universitari Vall d'Hebron, University of Iceland [Reykjavik], Università degli Studi di Milano = University of Milan (UNIMI), Universiteit Leiden-Universiteit Leiden, University of Pennsylvania-University of Pennsylvania, University of Pennsylvania, Georgetown University [Washington] (GU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universität Heidelberg [Heidelberg] = Heidelberg University, European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Human Genetics, Vall d'Hebron Barcelona Hospital Campus, Autonomous University of Barcelona, Universitat Autònoma de Barcelona [Barcelona] (UAB), Università degli studi di Milano [Milano], University Hospitals of Leicester, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, University of Pisa, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pomeranian Medical University-International Hereditary Cancer Centre, McGill University, University of Kansas Medical Center [Lawrence], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncology-University of Cambridge [UK] (CAM), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Università degli Studi di Roma 'La Sapienza' [Rome], IT University of Copenhagen, Laval University [Québec], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Pontificia Universidad Javeriana, University of Santiago de Compostela, Læknadeild (HÍ), Faculty of Medicine (UI), Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), MINES ParisTech - École nationale supérieure des mines de Paris, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Universidade do Porto, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea, Against Breast Cancer, Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea. H2020, Cancer UK Grant, Canadian Institutes of Health Research, Ministère de Économie, de la science et de innovation (Canadá), NIH - National Cancer Institute (NCI) (Estados Unidos), Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Xunta de Galicia (España), Canadian Cancer Society, California Breast Cancer Research Program, California Department of Public Health, Medical Research Council (Reino Unido), Free State of Saxony, Germany (LIFE -Leipzig Research Centre for Civilization Diseases), Federal Ministry of Education & Research (Alemania), German Cancer Aid, Helsinki University Central Hospital Research Fund, Finlands Akademi (Finlandia), Deutsche Forschungsgemeinschaft (Alemania), Russian Foundation for Basic Research, Ministry of Science and Higher Education (Rusia), National Health and Medical Research Council (Australia), Biobanking and BioMolecular resources Research Infrastructure (Países Bajos), Estée Lauder Companies’ Breast Cancer Campaign, Swedish Research Council, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Lon V. Smith Foundation, Research Coincil of Lithuania, Italian Association for Cancer Research, University of Kansas. Cancer Center (Estados Unidos), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), French National Cancer Institute, Netherlands Organisation for Health Research and Development, Pink Ribbons Project, United States of Department of Health & Human Services, HUS Gynecology and Obstetrics, Clinicum, University of Helsinki, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, University Management, HUS Comprehensive Cancer Center, Biosciences, Helsinki University Hospital, and Lietuvos Mokslo Taryba (Lituania)
Subjects: 0301 basic medicine, Gene mutation, Càncer - Aspectes genètics, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Mama - Càncer, Fanconi anemia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Brjóstakrabbamein, Medicine and Health Sciences, Pharmacology (medical), FANCM, 631/208/68, skin and connective tissue diseases, Cancer genetics, Triple-negative breast cancer, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Manchester Cancer Research Centre, Otros calificadores::Otros calificadores::/genética [Otros calificadores], article, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Life Sciences & Biomedicine, 3122 Cancers, ABCTB Investigators, lcsh:RC254-282, KConFab, Olaparib, Càncer de mama, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, SDG 3 - Good Health and Well-being, 631/67/68, medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Erfðafræði, Radiology, Nuclear Medicine and imaging, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ddc:610, Risk factor, CHEK2, Krabbamein, Cancer och onkologi, FancM, Science & Technology, cancer, MUTATIONS, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Biology and Life Sciences, nutritional and metabolic diseases, cancer genetics, medicine.disease, GENE, Expressió gènica, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], 030104 developmental biology, chemistry, 692/4028/67/68, Cancer and Oncology, FANCONI-ANEMIA, Cancer research, gene expression, C.5791C-GREATER-THAN-T, business
Abstract: Publisher's version (útgefin grein), Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors., Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the “Fondo Europeo de Desarrollo Regional, una manera de hacer Europa” (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB “Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina” Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika” Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d’Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d’Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O’Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O’Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union’s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l’Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l’Alimentation, de l’Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the ‘Stichting tegen Kanker’. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov” and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education “Regional Initiative of Excellence” in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’) to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d’Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5 × 1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women’s Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.
Published: 2019

32. Computational tools to detect signatures of mutational processes in DNA from tumours: a review and empirical comparison of performance

Author: Hanane Omichessan, Vittorio Perduca, Gianluca Severi, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Centre for Epidemiology and Biostatistics [Victoria, Australia], University of Melbourne-Melbourne School of Population and Global Health [Victoria, Australia], Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], University of Melbourne-Melbourne School for Population and Global Health, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Perduca, Vittorio, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Empirical comparison, Computer science, Somatic cell, Science, DNA Mutational Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, medicine.disease_cause, Genome, 03 medical and health sciences, chemistry.chemical_compound, Germline mutation, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer genome, Neoplasms, medicine, Humans, Exome sequencing, 030304 developmental biology, [STAT.AP]Statistics [stat]/Applications [stat.AP], 0303 health sciences, Mutation, Multidisciplinary, Mutation Spectra, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], COSMIC cancer database, Genome, Human, Computational Biology, DNA, Neoplasm, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Identification (information), chemistry, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Medicine, DNA, Algorithms, Research Article
Abstract: International audience; Mutational signatures refer to patterns in the occurrence of somatic mutations that might be uniquely ascribed to particular mutational process. Tumour mutation catalogues can reveal mutational signatures but are often consistent with the mutation spectra produced by a variety of mutagens. To date, after the analysis of tens of thousands of exomes and genomes from about 40 different cancer types, tens of mutational signatures characterized by a unique probability profile across the 96 trinucleotide-based mutation types have been identified , validated and catalogued. At the same time, several concurrent methods have been developed for either the quantification of the contribution of catalogued signatures in a given cancer sequence or the identification of new signatures from a sample of cancer sequences. A review of existing computational tools has been recently published to guide researchers and practitioners through their mutational signature analyses, but other tools have been introduced since its publication and, a systematic evaluation and comparison of the performance of such tools is still lacking. In order to fill this gap, we have carried out an empirical evaluation of the main packages available to date, using both real and simulated data. Among other results, our empirical study shows that the identification of signatures is more difficult for cancers characterized by multiple signatures each having a small contribution. This work suggests that detection methods based on probabilistic models, especially EMu and bayesNMF, have in general better performance than NMF-based methods.
Published: 2018
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33. Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort

Author: Roel Vermeulen, J. Ramón Quirós, Torkjel M. Sandanger, Domenico Palli, Carlotta Sacerdote, Gianluca Severi, Eva Ardanaz, Bas Bueno-de-Mesquita, Sara Grioni, Malin Sund, Rudolf Kaaks, Manuela M. Bergmann, Matthias B. Schulze, Federico Canzian, Miguel Rodríguez-Barranco, Luca Morelli, Carlo La Vecchia, Pietro Ferrari, Salvatore Panico, Anna Karakatsani, Theron Johnson, Pilar Amiano, Kay-Tee Khaw, Nicholas J. Wareham, Paula Jakszyn, Sandra Colorado-Yohar, Daniele Campa, Marie-Christine Boutron-Ruault, Julie A. Schmidt, Rosario Tumino, Anne Tjønneland, Verena Katzke, Vittorio Perduca, Manuel Gentiluomo, Antonia Trichopoulou, Elisabete Weiderpass, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Danish Cancer Society, Cancer Epidemiology Centre, Cancer Council Victoria, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Nutrition and Metabolism Section, International Agency for Research on Cancer, Deutsches Krebsforschungszentrum, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Dept of Epidemiology, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), Istituto per lo Studio e la Prevezione Oncologica, Partenaires INRAE, Epidemiology, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Civile - M.P.Arezzo Hospital, CPO Piemonte, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Division of Environmental Epidemiology, Utrecht University [Utrecht]-Institute of Risk Assessment Sciences, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Surgery and Perioperative Sciences, Umea University Hospital, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L´Hospitallet de Llobregat, Department of Pathology, Santa Chiara Hospital, Department of Cancer Epidemiology, One Health Chemisch, dIRAS RA-2, Gentiluomo, Manuel [0000-0002-0366-9653], Katzke, Verena A [0000-0002-6509-6555], Tjønneland, Anne [0000-0003-4385-2097], Perduca, Vittorio [0000-0003-0339-0473], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Weiderpass, Elisabete [0000-0003-2237-0128], Johnson, Theron [0000-0003-4850-282X], Bergmann, Manuela [0000-0001-5064-227X], Karakatsani, Anna [0000-0002-3275-2026], La Vecchia, Carlo [0000-0003-1441-897X], Palli, Domenico [0000-0002-5558-2437], Grioni, Sara [0000-0002-5891-8426], Tumino, Rosario [0000-0003-2666-414X], Ardanaz, Eva [0000-0001-8434-2013], Schmidt, Julie A [0000-0002-7733-8750], Morelli, Luca [0000-0002-7742-9556], Canzian, Federico [0000-0002-4261-4583], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Mitochondrial DNA, Pancreatic ductal adenocarcinoma, DNA Copy Number Variations, Epidemiology, EPIC, Real-Time Polymerase Chain Reaction, DNA, Mitochondrial, Risk Assessment, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Pancreatic cancer, medicine, Biomarkers, Tumor, Leukocytes, Humans, Copy-number variation, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, 2. Zero hunger, business.industry, Incidence, Age Factors, Middle Aged, Protective Factors, medicine.disease, Peripheral blood, 3. Good health, Mitochondria, Europe, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business
Abstract: Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10−5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16–0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07–0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.
Published: 2020

34. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Author: Douglas F. Easton, T.M. Mooij, Christian F. Singer, Lenka Foretova, Matti A. Rookus, Karin Kast, Kai-ren Ong, Louise Izatt, Jessica Moretta-Serra, Margreet G. E. M. Ausems, Diana Eccles, Patrick J. Morrison, Jan C. Oosterwijk, Mary B. Daly, Alex Henderson, Rita K. Schmutzler, Ana Osorio, Charlotte J. Dommering, Anne-Marie Gerdes, Marie Navratilova, Ibccs, Carole Brewer, Mieke Kriege, Mary Beth Terry, Christoph Engel, D. Gareth Evans, Edith Olah, Jackie Cook, David E. Goldgar, Anna Jakubowska, Antonis C. Antoniou, Jacques Simard, Laurence Gladieff, Catherine Noguès, Esther M. John, Brita Arver, Håkan Olsson, Jasmine A. McDonald, Irene L. Andrulis, Nadine Andrieu, Munaza Ahmed, Yen Y. Tan, Yuyan Liao, Embrace, Genepso, Bcfr, Hebon, kConFab, Trinidad Caldés, Véronique Mari, Roger L. Milne, Michael Friedlander, Elisabeth Luporsi, John L. Hopper, Marie-José Roos-Blom, Flora E. van Leeuwen, Sue-Anne McLachlan, Saundra S. Buys, Debra Frost, Daniel Barrowdale, Bruno Buecher, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Columbia University [New York], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Service de Génétique Oncologique, Institut Curie [Paris], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Claudius Regaud, Centre Alexis Vautrin (CAV), Newcastle Upon Tyne Hospitals NHS Trust, Department of Clinical Genetics, Royal Devon & Exeter Hospital, St Mary's Hospital, Wessex Clinical Genetics Service, Princess Anne Hospital, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Northern Ireland Regional Genetics Centre, Belfast City Hospital, Department of Clinical Genetics and Human Genetics, VU University Medical Center [Amsterdam], Department of Genetics, Department of Medical Genetics, University Medical Center [Utrecht], Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Internal Medicine, Huntsman Cancer Institute, Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Epidemiology, Cancer Prevention Institute of California, Division of Population Science, Fox Chase Cancer Center, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Human Genetics Group, Spanish National Cancer Research Centre, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Laboratoire de Génomique des Cancers, Université Laval [Québec] (ULaval), Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, National Institute of Oncology, Masaryk University [Brno] (MUNI), Odense University Hospital, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Departments of Epidemiology and Molecular Pathology, The Netherlands Cancer Institute, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Netherlands Cancer Institute, Innovation et Développement dans l'Agriculture et l'Alimentation (UMR Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195), the Australian National Breast Cancer Foundation (IF 17), the National Health and Medical Research Council (454508, 288704, 145684), the US National Institute of Health (1RO1CA159868), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. MODSQUAD Czech Republic, Brno was supported by MH CZ—DRO (MMCI, 00209805) and by MEYS—NPS I - LO1413 to LF, MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research grants KTIA-OTKA CK80745 and NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. € Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society., European Project: 294576,EC:FP7:ERC,ERC-2011-ADG_20110310,RISK FACTORS CANCER(2012), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), MUMC+: DA KG Lab Centraal Lab (9), Universität Leipzig [Leipzig], Institut Curie, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CRLCC Institut Claudius Regaud, Sheffield Children's Hospital, Birmingham Women's Hospital Healthcare NHS Trust, Pomeranian Medical University-International Hereditary Cancer Centre, Laval University [Québec], Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre national d'études agronomiques des régions chaudes (CNEARC)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Andrieu, Nadine, Genetic and environmental risk factors for common malignant tumours especially breast cancer and melanoma. - RISK FACTORS CANCER - - EC:FP7:ERC2012-04-01 - 2017-03-31 - 294576 - VALID, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Columbia Mailman School of Public Health-Columbia University [New York], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Targeted Gynaecologic Oncology (TARGON), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, INDUCED-ABORTION, endocrine system diseases, BIRTH, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, SUSCEPTIBILITY, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, COHORT, Prospective cohort study, skin and connective tissue diseases, REPRODUCTIVE FACTORS, [SDV.GEN]Life Sciences [q-bio]/Genetics, PARITY, business.industry, Proportional hazards model, Obstetrics, Hazard ratio, Retrospective cohort study, medicine.disease, CARRIERS, OVARIAN, Confidence interval, [SDV] Life Sciences [q-bio], KCONFAB, 030104 developmental biology, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Cohort, COLLABORATIVE REANALYSIS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Breast feeding
Abstract: Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
Published: 2018

35. E-cadherin breast tumor expression, risk factors and survival:Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium

Author: Horne, Hisani N., Oh, Hannah, Sherman, Mark E., Palakal, Maya, Hewitt, Stephen M., Schmidt, Marjanka K., Milne, Roger L., Hardisson, David, Benitez, Javier, Blomqvist, Carl, Bolla, Manjeet K., Brenner, Hermann, Chang-Claude, Jenny, Cora, Renata, Couch, Fergus J., Cuk, Katarina, Devilee, Peter, Easton, Douglas F., Eccles, Diana M., Eilber, Ursula, Hartikainen, Jaana M., Heikkilä, Päivi, Holleczek, Bernd, Hooning, Maartje J., Jones, Michael, Keeman, Renske, Mannermaa, Arto, Martens, John W. M., Muranen, Taru A., Nevanlinna, Heli, Olson, Janet E., Orr, Nick, Perez, Jose I. A., Pharoah, Paul D. P., Ruddy, Kathryn J., Saum, Kai-Uwe, Schoemaker, Minouk J., Seynaeve, Caroline, Sironen, Reijo, Smit, Vincent T. H. B. M., Swerdlow, Anthony J., Tengström, Maria, Thomas, Abigail S., Timmermans, A. Mieke, Tollenaar, Rob A. E. M., Troester, Melissa A., van Asperen, Christi J., van Deurzen, Carolien H. M., Van Leeuwen, Flora F., Van’t Veer, Laura J., García-Closas, Montserrat, Figueroa, Jonine D., National Breast Cancer Foundation (Australia), Cancer Australia, National Institutes of Health (Estados Unidos), Cancer Research UK (Reino Unido), European Research Council, Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, Ministry of Science, Research and the Arts of Baden-Wuerttemberg (Alemania), German Cancer Aid, Finlands Akademi (Finlandia), Cancer Society of Finland, Nordic Cancer Union (Islandia), Sigrid Jusélius Foundation, Cancer Society of North Savo, Finnish Cancer Organizations, University of Eastern Finland (Finlandia), Cancer Council Queensland (Australia), Cancer Council New South Wales (Australia), Cancer Council Victoria (Australia), Cancer Council Tasmania (Australia), Cancer Council of South Australia (Australia), Cancer Council Western Australia (Australia), United States Army Medical Research and Development Command, National Health and Medical Research Council (Australia), NIH - National Cancer Institute (NCI) (Estados Unidos), Institute of Cancer Research (Reino Unido), Milne, Roger L [0000-0001-5764-7268], Hardisson, David [0000-0002-2183-3699], Easton, Douglas F [0000-0003-2444-3247], Martens, John WM [0000-0002-3428-3366], Nevanlinna, Heli [0000-0002-0916-2976], Pharoah, Paul DP [0000-0001-8494-732X], Figueroa, Jonine D [0000-0002-5100-623X], Apollo - University of Cambridge Repository, Medical Oncology, and Pathology
Subjects: Adult, Receptor, ErbB-2, lcsh:R, lcsh:Medicine, Gene Expression, Breast Neoplasms, Middle Aged, Cadherins, Prognosis, Article, Editorial, SDG 3 - Good Health and Well-being, Receptors, Estrogen, Risk Factors, Case-Control Studies, Biomarkers, Tumor, Odds Ratio, Journal Article, Humans, lcsh:Q, Female, lcsh:Science, Receptors, Progesterone, Aged, Proportional Hazards Models
Abstract: E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score
Published: 2018

36. Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

Author: Christian F. Singer, Louise Izatt, Yen Y. Tan, Emmanuelle Mouret-Fourme, Embrace, Genepso, Bcfr, Hebon, kConFab, Marie Navratilova, Lucy Side, Trinidad Caldés, Rosemarie Davidson, Kelly-Anne Phillips, Saundra S. Buys, Dominique Leroux, Mary B. Daly, Melissa C. Southey, Marian J.E. Mourits, Brita Arver, Theo A. M. van Os, Anne-Marie Gerdes, Douglas F. Easton, Marie-José Roos-Blom, Michael Friedlander, Lieske H. Schrijver, David E. Goldgar, Anna Jakubowska, Roger L. Milne, Håkan Olsson, Lisa Walker, Ros Eeles, Flora E. van Leeuwen, Mary Porteous, Sue-Anne McLachlan, Pascaline Berthet, Lenka Foretova, Catherine Noguès, Matti A. Rookus, Debra Frost, Daniel Barrowdale, Esther M. John, Julian Adlard, Encarna B. Gomez Garcia, Nadine Andrieu, Laurence Venat-Bouvet, Anita Bane, John L. Hopper, Mary Beth Terry, Jacques Simard, Ana Osorio, Antonis C. Antoniou, Christoph Engel, Wendy K. Chung, Karin Kast, Ibccs, D. Gareth Evans, Valérie Bonadona, Edith Olah, Steve Ellis, Christi J. van Asperen, T.M. Mooij, Human Genetics, APH - Methodology, APH - Quality of Care, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Skane University Hospital [Lund], Lund University [Lund], University of Melbourne, Columbia Mailman School of Public Health, University of Utah School of Medicine [Salt Lake City], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Department of Clinical Sciences [Lund], University of Leipzig [Leipzig, Allemagne], Chapel Allerton Hospital, University of Cambridge [UK] (CAM), Queen Elizabeth University Hospital (Glasgow), Royal Marsden NHS Foundation Trust, University of Manchester [Manchester], Guy's and St Thomas NHS Foundation Trust [London], Western General Hospital [Edinburgh, UK], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK], Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire [Grenoble] (CHU), hôpital couple-enfant [CHU Grenoble Alpes], Hôpital René HUGUENIN (Saint-Cloud), Hôpital Dupuytren [CHU Limoges], Huntsman Cancer Institute [Salt Lake City], University of Utah, Monash University [Melbourne], Stanford University School of Medicine [CA, USA], California Sciences Institute, Columbia University [New York], Fox Chase Cancer Center, McMaster University [Hamilton, Ontario], Karolinska Institutet [Stockholm], Leiden University Medical Center (LUMC), School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Medical Center Groningen [Groningen] (UMCG), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, St. Vincent's Hospital, Sydney, Medizinische Universität Wien = Medical University of Vienna, Masaryk Memorial Cancer Institute (RECAMO), University Hospital of Cologne [Cologne], Copenhagen University Hospital, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Université Laval [Québec] (ULaval), National Institute of Oncology [Budapest, Hungary], Pomeranian Medical University [Szczecin, Poland] (PMU), Spanish National Cancer Centre, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], Melbourne School for Population and Global Health-University of Melbourne, Leipzig University, Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Masaryk Memorial Cancer Institute (MMCI), Pomeranian Medical University [Szczecin] (PUM), Mines Paris - PSL (École nationale supérieure des mines de Paris), University of Melbourne-Melbourne School for Population and Global Health, Malbec, Odile, Universiteit Leiden, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, MUMC+: DA KG Lab Centraal Lab (9), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Life Course Epidemiology (LCE), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Article, OVARIAN-CANCER, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, medicine, Prospective cohort study, skin and connective tissue diseases, Pregnancy, Proportional hazards model, Obstetrics, business.industry, Hazard ratio, CONSORTIUM, WOMEN, medicine.disease, PREVENTION, Confidence interval, KCONFAB, [SDV] Life Sciences [q-bio], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business, Cohort study
Abstract: Background For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear. Methods Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed. Results For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P < .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002). Conclusions Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40–50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and nonhormonal contraceptive methods should be discussed.
Published: 2018

37. Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case?control study

Author: Deltour, Isabelle, Schlehofer, Brigitte, Massardier-Pilonchery, Amelie, Schlaefer, Klaus, Armstrong, Bruce, Giles, Graham G., Siemiatycki, Jack, Parent, Marie-Elise, Krewski, Daniel, McBride, Mary, Johansen, Christoffer, Auvinen, Anssi, Salminen, Tiina, Hours, Martine, Montestrucq, Lucile, Blettner, Maria, Berg-Beckhoff, Gabriele, Sadetzki, Siegal, Chetrit, Angela, Lagorio, Susanna, Iavarone, Ivano, Yamaguchi, Naohito, Takebayashi, Toru, Woodward, Alistair, Cook, Angus, Tynes, Tore, Klaeboe, Lars, Feychting, Maria, Lonn, Stefan, Fleming, Sarah, Swerdlow, Anthony J., Schoemaker, Minouk J., Moissonnier, Monika, Kesminiene, Ausrele, Cardis, Elisabeth, Schuz, Joachim, Vrijheid, M., Evrard, A-S, Sanchez, M., Brown, J., Nadon, L., Christensen, H. C., Kurttio, P., Lahkola, A., Bernard, M., Jarus-Hakak, A., Pearce, N., Blaasaas, K., Ahlbom, A., McKinney, Patricia A., Muir, K. R., Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Unit of Environmental Epidemiology, German Cancer Research Center, Heidelberg, Germany, parent, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), School of Public Health, The University of Sydney, Sydney, Australia, Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia, University of Montreal School of Public Health, Montreal, Canada, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Canada, and British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, Canada
Subjects: Adult, Male, medicine.medical_specialty, Population, INTERNATIONAL, Audiology, NOISE, 03 medical and health sciences, 0302 clinical medicine, Occupational Exposure, Recall bias, Epidemiology, Humans, Medicine, EPIDEMIOLOGY, EXPOSURE, education, Vestibular system, education.field_of_study, ACOUSTIC NEUROMA, NOISE EXPOSURE, business.industry, Public Health, Environmental and Occupational Health, Case-control study, Neuroma, Acoustic, Odds ratio, case‒control study, Middle Aged, LOUD NOISE, 030210 environmental & occupational health, Confidence interval, VESTIBULAR SCHWANNOMA, Noise, BRUIT, CASE CONTROL STUDY, INTERPHONE, Noise, Occupational, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Public aspects of medicine, RA1-1270, business
Abstract: Objective Studies of loud noise exposure and vestibular schwannomas (VS) have shown conflicting results. The population-based INTERPHONE case‒control study was conducted in 13 countries during 2000-2004. In this paper, we report the results of analyses on the association between VS and self-reported loud noise exposure. Methods Self-reported noise exposure was analyzed in 1024 VS cases and 1984 matched controls. Life-long noise exposure was estimated through detailed questions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted conditional logistic regression for matched sets. Results The OR for total work and leisure noise exposure was 1.6 (95% CI 1.4-1.9). OR were 1.5 (95% CI 1.3-1.9) for only occupational noise, 1.9 (95% CI 1.4-2.6) for only leisure noise and 1.7 (95% CI 1.2-2.2) for exposure in both contexts. OR increased slightly with increasing lag-time. For occupational exposures, duration, time since exposure start and a metric combining lifetime duration and weekly exposure showed significant trends of increasing risk with increasing exposure. OR did not differ markedly by source or other characteristics of noise. Conclusion The consistent associations seen are likely to reflect either recall bias or a causal association, or potentially indicate a mixture of both.
Published: 2018

38. Interactions between occupational exposure to extremely low frequency magnetic fields and chemicals for brain tumour risk in the INTEROCC study

Author: Daniel Krewski, Elisabeth Cardis, Joseph D. Bowman, Dave McLean, Brigitte Schlehofer, Michelle C. Turner, Laurel Kincl, Klaus Schlaefer, Jordi Figuerola, Martine Hours, Siegal Sadetzki, Martie van Tongeren, Sarah Fleming, Marie-Élise Parent, Geza Benke, Jack Siemiatycki, Lesley Richardson, Joachim Schüz, CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), McLaughlin Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], Monash University [Clayton], National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention (CDC), University of Leeds, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Oregon State University (OSU), School of Epidemiology, Public Health and Disease Prevention, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Chaim Sheba Medical Center, Tel Aviv University [Tel Aviv], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institute of Occupational Medicine [Edinburgh] (IOM), The INTEROCC study was funded by the National Institutes for Health (NIH) Grant No 1R01CA124759 (PI E Cardis). Coding of the French occupational data was in part funded by AFSSET (Convention No ST-2005-004). The INTERPHONE study was supported by funding from the European Fifth Framework Program, ‘Quality of Life and Management of Living Resources’ (contract 100 QLK4-CT-1999901563) and the International Union against Cancer (UICC). In Australia,funding was received from the Australian National Health and Medical ResearchCouncil (EME Grant 219129) with funds originally derived from mobile phone service license fees, a University of Sydney Medical Foundation Program, the Cancer Council NSW and The Cancer Council Victoria. In Canada funding was received from the Canadian Institutes of Health Research (project MOP-42525), he Canada Research Chair programme, the Guzzo-CRS Chair in Environment and Cancer, the Fonds de larecherche en santé du Québec, the Canadian Institutes of Health Research(CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association, the NSERC Chair in Risk Science at the University of Ottawa. In France, funding was received by l’Association pour la Recherche sur le Cancer (ARC) (ContratN85142) and three network operators (Orange, SFR, Bouygues Telecom). In Germany, funding was received from the German Mobile Phone Research Program (Deutsches Mobilfunkforschungsprogramm) of the German Federal Ministry for the Environment, Nuclear Safety, and Nature Protection, the Ministry for the Environment and Traffic of the state of Baden-Wurttemberg, the Ministry for the Environment of the state of North Rhine-Westphalia, the MAIFOR Program (Mainzer Forschungsforderungsprogramm) of the University of Mainz. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation, the Wellington Medical Research Foundation, the Waikato Medical Research Foundation and the Cancer Society of New Zealand. Additional funding for the UK study was received from the Mobile Telecommunications, Health andResearch (MTHR) programme, funding from the Health and Safety Executive, the Department of Health, the UK Network Operators (O2, Orange, T-Mobile, Vodafone, ‘3’) and the Scottish Executive, European Project: 1999901563,QLK4-CT, Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), and Tel Aviv University (TAU)
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Pathology, Canada, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Lower risk, meningioma, Article, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Electromagnetic Fields, Time windows, Risk Factors, Internal medicine, Glioma, Occupational Exposure, glioma, medicine, Journal Article, Meningeal Neoplasms, occupation, Humans, 030212 general & internal medicine, Israel, Aged, Australasia, business.industry, Brain Neoplasms, Public Health, Environmental and Occupational Health, Middle Aged, medicine.disease, Europe, Occupational Diseases, Logistic Models, Magnetic Fields, 030220 oncology & carcinogenesis, Case-Control Studies, Etiology, Conditional logistic regression, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Occupational exposure, business
Abstract: International audience; In absence of clear evidence regarding possible effects of occupational chemical exposures on brain tumour aetiology, it is worthwhile to explore the hypothesis that such exposures might act on brain tumour risk in interaction with occupational exposure to extremely low frequency magnetic fields (ELF).INTEROCC is a seven-country (Australia, Canada, France, Germany, Israel, New Zealand and UK), population-based, case-control study, based on the larger INTERPHONE study. Incident cases of primary glioma and meningioma were ascertained from 2000 to 2004. Job titles were coded into standard international occupational classifications and estimates of ELF and chemical exposures were assigned based on job-exposure matrices. Dichotomous indicators of cumulative ELF (≥50th vs
Published: 2017

39. Occupational solvent exposure and risk of glioma in the INTEROCC study

Author: Klaus Schlaefer, Martie van Tongeren, Daniel Krewski, Jack Siemiatycki, Maria Blettner, Geza Benke, Jordi Figuerola, Sarah Fleming, Martine Hours, Elisabeth Cardis, Michelle C. Turner, Lesley Richardson, Laurel Kincl, Marie-Élise Parent, Siegal Sadetzki, Brigitte Schlehofer, David McLean, Monash University [Clayton], Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), University of Ottawa [Ottawa], University of Leeds, Oregon State University (OSU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Sackler Faculty of Medicine, Tel Aviv University (TAU), Chaim Sheba Medical Center, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institute of Occupational Medicine [Edinburgh] (IOM), University of Manchester [Manchester], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), This work was funded by the National Institutes for Health (NIH) Grant No. 1R01CA124759-01. Coding of the French occupational data was in part funded by AFSSET (Convention No. ST-2005-004). The INTERPHONE study was supported by funding from the European Fifth Framework Program, ‘Quality of Life and Management of Living Resources’ (contract 100 QLK4-CT-1999901563) and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers’ Forum and GSM Association. In Australia, funding was received from the Australian National Health and Medical Research 5 Council (EME Grant 219129) with funds originally derived from mobile phone service licence fees, a University of Sydney Medical Foundation Program, the Cancer Council NSW and The Cancer Council Victoria. In Canada, funding was received from the Canadian Institutes of Health Research (project MOP-42525), the Canada Research Chair programme, the Guzzo-Cancer Research Society Chair in Environment and Cancer, the Fonds de la recherche en sante du Quebec, the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association, and the NSERC/SSHRC/McLaughlin Chair in Population Health Risk Assessment at the University of Ottawa. In France, funding was received by l’Association pour la Recherche sur le Cancer (ARC) (Contrat N85142) and three network operators (Orange, SFR, Bouygues Telecom). In Germany, funding was received from the German Mobile Phone Research Program (Deutsches Mobilfunkforschungsprogramm) of the German Federal Ministry for the Environment, Nuclear 45 Safety, and Nature Protection, the Ministry for the Environment and Traffic of the state of Baden-Wurttemberg, the Ministry for the Environment of the state of North Rhine-Westphalia, and the MAIFOR Program (Mainzer Forschungsforderungsprogramm) of the University of Mainz. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation, the Wellington Medical Research Foundation, the Waikato Medical Research Foundation and the Cancer Society of New Zealand. Additional funding for the UK study was received from the Mobile Telecommunications, Health and Research (MTHR) program, funding from the Health and Safety Executive, the Department of Health, the UK Network Operators (O2, Orange, T-Mobile, Vodafone, ‘3’) and the Scottish Executive. Michelle C Turner was funded by a Government of Canada Banting Postdoctoral Fellowship., European Project: 1999901563,QLK4-CT, Johannes Gutenberg - Universität Mainz (JGU), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), and Tel Aviv University [Tel Aviv]
Subjects: Male, Oncology, MESH: United Kingdom, Cancer Research, Epidemiology, [SDV]Life Sciences [q-bio], MESH: Neoplasm Grading, MESH: Solvents, MESH: Occupational Exposure, MESH: Glioma, Tumor grade, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, MESH: New Zealand, MESH: Risk Factors, Germany, Odds Ratio, Israel, Young adult, MESH: Aged, Occupation, MESH: Middle Aged, Brain Neoplasms, Age Factors, MESH: Israel, Glioma, Middle Aged, 030210 environmental & occupational health, MESH: Case-Control Studies, 3. Good health, MESH: Young Adult, 030220 oncology & carcinogenesis, Solvent, MESH: Brain Neoplasms, Female, France, Adult, Canada, medicine.medical_specialty, Adolescent, Case–control study, Job-exposure matrix, MESH: Australia, Young Adult, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, MESH: Canada, Occupational Exposure, Internal medicine, medicine, Journal Article, Humans, MESH: Germany, Aged, MESH: Adolescent, MESH: Age Factors, MESH: Humans, business.industry, Australia, Case-control study, MESH: Adult, Odds ratio, medicine.disease, United Kingdom, Confidence interval, MESH: Male, MESH: Odds Ratio, MESH: France, chemistry, Case-Control Studies, Solvents, Neoplasm Grading, Solvent exposure, business, MESH: Female, New Zealand
Abstract: BACKGROUND: The aetiology of glioma remains largely unknown. Occupational solvent exposure has been suggested as a putative cause of glioma, but past studies have been inconsistent. We examined the association between a range of solvents and glioma risk within the INTEROCC project, a study of brain tumours and occupational exposures based on data from seven national case-control studies conducted in the framework of the INTERPHONE study. We also investigated associations according to tumour grade.METHODS: Data from the seven countries were standardised and then combined into one aggregate data set. Pooled odds ratios (ORs) were estimated for adjusted models that included sex, age, country-region of residence and level of educational attainment. Exposures to any solvent or 11 specific solvents or subgroups were assessed using a modified version of the FINJEM job exposure matrix (JEM) specifically developed for the study, called INTEROCC-JEM.RESULTS: Analysis included 2000 glioma cases and 5565 controls. For glioma and ever/never exposure to any solvent, the OR was 0.91 (95% confidence interval: 0.74-1.11). All ORs were CONCLUSIONS: The results of this study show no consistent associations for any solvent exposures overall or by grade of tumour.British Journal of Cancer advance online publication 14 September 2017; doi:10.1038/bjc.2017.285 www.bjcancer.com.
Published: 2017

40. Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case-control study

Author: Parent, Marie-Elise, TURNER, Michelle C., LAVOUE, Jérôme, Richard, Hugues, Figuerola, Jordi, KINCL, Laurel, Richardson, Lesley, BENKE, Geza, Blettner, Maria, FLEMING, Sarah, Hours, Martine, KREWSKI, Daniel, McLean, David, SADETZKI, Siegal, Schlaefer, Klaus, SCHLEHOFER, Brigitte, Schüz, Joachim, Siemiatycki, Jack, VAN TONGEREN, Martie, Cardis, Elisabeth, Parent, Marie-Élise, Turner, Michelle, Lavoué, Jérôme, Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Universitat Pompeu Fabra [Barcelona] (UPF), Université de Montréal (UdeM), Oregon State University (OSU), Centre Hospitalier de l'Université de Montréal (CHUM), Monash University [Melbourne], Johannes Gutenberg - Universität Mainz (JGU), University of Leeds, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), University of Ottawa [Ottawa], Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Unit of Environmental Epidemiology, Deutsches Krebsforschungszentrum, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Hospital Research Centre, Institute of Occupational Medicine [Edinburgh] (IOM), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, This work was funded by the National Institutes for Health (NIH) Grant No. 1R01CA124759–01. Coding of the French occupational data was in part funded by AFSSET (Convention N° ST-2005-004). The INTERPHONE study was supported by funding from the European Fifth Framework Program, ‘Quality of Life and Management of Living Resources’ (contract 100 QLK4-CT-1999901563) and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers’ Forum and GSM Association. In Australia, funding was received from the Australian National Health and Medical Research Council (EME Grant 219,129) with funds originally derived from mobile phone service licence fees, a University of Sydney Medical Foundation Program, the Cancer Council NSW and The Cancer Council Victoria. In Canada funding was received from the Canadian Institutes of Health Research (CIHR) (project MOP-42525), the Canada Research Chair programme, the Guzzo-Cancer Research Society Chair in Environment and Cancer, the Fonds de la recherche du Québec - Santé, CIHR with partial support from the Canadian Wireless Telecommunications Association, the NSERC Chair in Population Risk Science at the University of Ottawa. In France, funding was received by l’Association pour la Recherche sur le Cancer (ARC) (Contract N85142) and three network operators (Orange, SFR, Bouygues Telecom). In Germany, funding was received from the German Mobile Phone Research Program (Deutsches Mobilfunkforschungsprogramm) of the German Federal Ministry for the Environment, Nuclear 45 Safety, and Nature Protection, the Ministry for the Environment and Traffic of the state of Baden- Wuerttemberg, the Ministry for the Environment of the state of North Rhine-Westphalia, the MAIFOR Program (Mainzer Forschungsforderungsprogramm) of the University of Mainz. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation, the Wellington Medical Research Foundation, the Waikato Medical Research Foundation and the Cancer Society of New Zealand. Additional funding for the UK study was received from the Mobile Telecommunications, Health and Research (MTHR) program, funding from the Health and Safety Executive, the Department of Health, the UK Network Operators (O2, Orange, T-Mobile, Vodafone, ‘3′) and the Scottish Executive., European Project: 1999901563,QLK4-CT, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)
Subjects: Health, Toxicology and Mutagenesis, Cumulative Exposure, Logistic regression, MESH: Occupational Exposure, MESH: Glioma, 610 Medical sciences Medicine, 0302 clinical medicine, MESH: Welding, Medicine, Welding, MESH: Risk, Occupational exposures, Incidence (epidemiology), lcsh:Public aspects of medicine, Glioma, MESH: Metals, Heavy, 030210 environmental & occupational health, 3. Good health, Occupational Diseases, Metals, 030220 oncology & carcinogenesis, lcsh:Industrial medicine. Industrial hygiene, Gases, Metalls, MESH: Occupational Diseases, Risk, Job-exposure matrix, [SDV.CAN]Life Sciences [q-bio]/Cancer, Air Pollutants, Occupational, MESH: Air Pollutants, Occupational, 03 medical and health sciences, lcsh:RC963-969, Environmental health, Metals, Heavy, Occupational Exposure, Journal Article, EXPOSITION AU RISQUE, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Gases, business.industry, Research, Public Health, Environmental and Occupational Health, Case-control study, lcsh:RA1-1270, Odds ratio, INTEROCC, medicine.disease, Confidence interval, Welding fumes, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: BACKGROUND: Brain tumor etiology is poorly understood. Based on their ability to pass through the blood-brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent. METHODS: We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30-69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM. RESULTS: In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7-1.0) for lead to 1.1 (0.7-1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted. CONCLUSIONS: Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma.
Published: 2017

41. Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC)

Author: John J. Spinelli, Graham G. Giles, Parveen Bhatti, Alexandra Nieters, Dennis D. Weisenburger, Anneclaire J. De Roos, Lenka Foretova, Paolo Boffetta, Mark P. Purdue, Nikolaus Becker, Nicola J. Camp, Brian C.-H. Chiu, Marc Maynadié, Guido Tricot, Silvia de Sanjosé, Pier Luigi Cocco, Dalsu Baris, Yawei Zhang, Veronique Benhaim-Luzon, Kirsten B. Moysich, Laura Costas, Anthony Staines, Elizabeth E. Brown, Wendy Cozen, Paul Brennan, Brenda M. Birmann, Gabriella Andreotti, Brigham and Women's Hospital [Boston], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), CIBER de Epidemiología y Salud Pública (CIBERESP), Facultat de Medicina [Barcelona], Catalan Institute of Oncology, Masaryk University [Brno] (MUNI), The Cancer Council Victoria, Université de Bourgogne (UB), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Registre des hémopathies malignes de Côte d'Or, Department of Cancer Prevention and Control, Roswell Park Cancer Institute [Buffalo], Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, University of Iowa [Iowa City], Department of Pathology (City of Hope, Duarte, California), City of Hope Comprehensive Cancer Center [Duarte], Yale School of Public Health (YSPH), Yale University School of Medicine, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, German Cancer Research Center [Heidelberg] ( DKFZ ), Helmholtz-Gemeinschaft, Masaryk University, Université de Bourgogne ( UB ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Department of Internal Medicine, University of Iowa, Iowa City, Iowa, Yale School of Public Health ( YSPH ), Yale School of Medicine, and Birmann, B.M. and Andreotti, G. and De Roos, A.J. and Camp, N.J. and Chiu, B.C.H. and Spinelli, J.J. and Becker, N. and Benhaim-Luzon, V. and Bhatti, P. and Boffetta, P. and Brennan, P. and Brown, E.E. and Cocco, P. and Costas, L. and Cozen, W. and De Sanjose, S. and Foretova, L. and Giles, G.G. and Maynadie, M. and Moysich, K. and Nieters, A. and Staines, A. and Tricot, G. and Weisenburger, D. and Zhang, Y. and Baris, D. and Purdue, M.P.
Subjects: 0301 basic medicine, Male, obesity, procedure, Epidemiology, groups by age, Overweight, cancer risk, Body Mass Index, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, study design, Risk Factors, middle aged, Young adult, risk factor, Adult, Multiple myeloma, 2. Zero hunger, education.field_of_study, anthropometry, adult, risk assessment, 3. Good health, multiple myeloma, female, Oncology, priority journal, 030220 oncology & carcinogenesis, young adult, medicine.symptom, Case-Control Studie, medicine.medical_specialty, multivariate logistic regression analysi, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, human, education, Aged, business.industry, Case-control study, Anthropometry, case control study, medicine.disease, Confidence interval, 030104 developmental biology, Endocrinology, Case-Control Studies, pathology, business, Body mass index, body ma
Abstract: Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case–control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI.Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls.Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04–1.14; P = 0.007]. We observed significant heterogeneity by study design (P = 0.04), noting the BMI–multiple myeloma association only for population-based studies (Ptrend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m2; OR, 1.2; 95% CI, 1.1–1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI (Pinteraction Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood.Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876–85. ©2017 AACR.
Published: 2017

42. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Author: Law, Philip J, Berndt, Sonja I, Speedy, Helen E, Camp, Nicola J, Sava, Georgina P, Skibola, Christine F, Holroyd, Amy, Joseph, Vijai, Sunter, Nicola J, Nieters, Alexandra, Bea, Silvia, Monnereau, Alain, Martin-Garcia, David, Goldin, Lynn R, Clot, Guillem, Teras, Lauren R, Quintela, Inés, Birmann, Brenda M, Jayne, Sandrine, Cozen, Wendy, Majid, Aneela, Smedby, Karin E, Lan, Qing, Dearden, Claire, Brooks-Wilson, Angela R., Hall, Andrew G, Purdue, Mark P, Mainou-Fowler, Tryfonia, Vajdic, Claire M, Jackson, Graham H, Cocco, Pierluigi, Marr, Helen, Zhang, Yawei, Zheng, Tongzhang, Giles, Graham G, Lawrence, Charles, Call, Timothy G, Liebow, Mark, Melbye, Mads, Glimelius, Bengt, Mansouri, Larry, Glenn, Martha, Curtin, Karen, Diver, W Ryan, Link, Brian K, Conde, Lucia, Bracci, Paige M., Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, McKay, James, Albanes, Demetrius, Weinstein, Stephanie, Wang, Zhaoming, Caporaso, Neil E., Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Vermeulen, Roel C H, Southey, Melissa C, Milne, Roger L., Clavel, Jacqueline, Topka, Sabine, Spinelli, John J, Kraft, Peter, Ennas, Maria Grazia, Summerfield, Geoffrey, Ferri, Giovanni M, Harris, Robert J, Miligi, Lucia, Pettitt, Andrew R, North, Kari E, Allsup, David J, Fraumeni, Joseph F, Bailey, James R, Offit, Kenneth, Pratt, Guy, Hjalgrim, Henrik, Pepper, Christopher, Chanock, Stephen J, Fegan, Chris, Rosenquist, Richard, de Sanjose, Silvia, Carracedo, Angel, Dyer, Martin J S, Catovsky, Daniel, Campo, Elias, Cerhan, James R., Allan, James M, Rothman, Nathanial, Houlston, Richard, Slager, Susan, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Department of Physics, Loyola College, Nungambakkam, Chennai – 600 034, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Aleppo [Aleppo], Sea Mammal Research Unit [University of St Andrews] (SMRU), School of Biology [University of St Andrews], University of St Andrews [Scotland]-University of St Andrews [Scotland]-Natural Environment Research Council (NERC), Department of Chemical Engineering, Imperial College London, De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (MONARIS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), The Cancer Council Victoria, University of Oulu, Uppsala Universitet [Uppsala], Université Paris Nanterre (UPN), University of Iowa [Iowa City], Registre des hémopathies malignes de Côte d'Or, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), B.B. Brodie Department of Neuroscience, Pennsylvania State University (Penn State), Penn State System, University of Newcastle [Australia] (UoN), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Department of Haematology, School of Medicine, Cardiff University, CIBER de Enfermedades Raras (CIBERER), University of Leeds, Haemato-oncology, Institute of cancer research, Mayo Clinic [Rochester], Northern Institute for Cancer Research [Newcastle] (NICR), Newcastle University [Newcastle], Institute of Cancer Research, Belmont, Sutton, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Sea Mammal Research Unit, Scottish Oceans Institute, University of St Andrews [Scotland], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Cardiff, Équipe Instrumentation embarquée et systèmes de surveillance intelligents (LAAS-S4M), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), University of Newcastle [Callaghan, Australia] (UoN), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-2, Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: Adult, Male, RM, Cancer och onkologi, B-Lymphocytes, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Science, Chromosome Mapping, Middle Aged, Leukemia, Lymphocytic, Chronic, B-Cell, Polymorphism, Single Nucleotide, Article, Young Adult, Cancer and Oncology, Case-Control Studies, Antibody Formation, Chromosomes, Human, Humans, Female, Genetic Predisposition to Disease, RC, Genome-Wide Association Study
Abstract: Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response., Chronic lymphocytic leukaemia has a hereditary component, much of which remains to be identified. Here, the authors perform a genome-wide association study and find new risk loci for the disease, which are associated with genes involved in immune function.
Published: 2017

43. Investigation of bias related to differences between case and control interview dates in five INTERPHONE countries

Author: Siegal Sadetzki, Alistair Woodward, Mary L. McBride, Daniel Krewski, Elisabeth Cardis, Michelle C. Turner, Lesley Richardson, Angela Chetrit, Jordi Figuerola, Graham G. Giles, Jack Siemiatycki, Bruce K. Armstrong, Rodrigo Villegas, Martine Hours, Marie-Élise Parent, Chelsea Eastman Langer, CIBER de Epidemiología y Salud Pública (CIBERESP), University of Ottawa [Ottawa], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Chaim Sheba Medical Center, The University of Sydney, Cancer Epidemiology Centre, Cancer Council Victoria, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), British Columbia Cancer Agency, Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), School of Population Health, and University of Auckland [Auckland]
Subjects: Adult, Male, medicine.medical_specialty, Matching (statistics), Canada, Time Factors, Operations research, Epidemiology, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Matched-Pair Analysis, Decile, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, Bias, Risk Factors, medicine, Odds Ratio, Humans, 030212 general & internal medicine, Israel, media_common, Selection bias, business.industry, Case-control study, Australia, Environmental exposure, Odds ratio, Environmental Exposure, Glioma, Middle Aged, Cellular telephone, 030220 oncology & carcinogenesis, Case-Control Studies, Epidemiologic Research Design, Female, France, MESH: Cellular telephone, Glioma, Matching, Case-control study, business, Cell Phone, Demography, New Zealand
Abstract: Purpose Associations between cellular telephone use and glioma risk have been examined in several epidemiological studies including the 13-country INTERPHONE study. Although results showed no positive association between cellular telephone use and glioma risk overall, no increased risk for long-term users, and no exposure-response relationship, there was an elevated risk for those in the highest decile of cumulative call time. However, results may be biased as data were collected during a period of rapidly increasing cellular telephone use, and as controls were usually interviewed later in time than cases. Methods Further analyses were conducted in a subset of five INTERPHONE study countries (Australia, Canada, France, Israel, New Zealand) using a post hoc matching strategy to optimize proximity of case-to-control interview dates and age. Results Although results were generally similar to the original INTERPHONE study, there was some attenuation of the reduced odds ratios and stronger positive associations among long-term users and those in the highest categories for cumulative call time and number of calls (eighth–ninth and 10th decile). Conclusions Proximity and symmetry in timing of case-to-control interviews should be optimized when exposure patterns are changing rapidly with time.
Published: 2016

44. Combined genetic and splicing analysis of BRCA1 c.[594-2A > C; 641A > G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms

Author: Barbara Wappenschmidt, Fergus J. Couch, Norbert Arnold, Claude Houdayer, Manjeet K. Bolla, Omar Soukarieh, Sean V. Tavtigian, Irene L. Andrulis, Alexandra Becker, Alexandra Martins, Qin Wang, Sara Margolin, Paolo Radice, Janet E. Olson, Mitul Shah, Juul T. Wijnen, Amanda B. Spurdle, Nichola Johnson, Carole Brewer, Harald Surowy, Graham G. Giles, Ana Blanco, Kamila Czene, Thomas Hansen, Wendy S. Rubinstein, Anja Rudolph, Christian F. Singer, Antonis C. Antoniou, Douglas F. Easton, Fiona M. Blows, Michael T. Parsons, kConFab Investigators, Annika Lindblom, Nicola K. Poplawski, Melissa C. Southey, Emily Hallberg, Vanessa Lattimore, Yvette van Ierland, Logan C. Walker, Joe Dennis, Gord Glendon, Ana Vega, Diether Niederacher, Laurent Castera, David E. Goldgar, Ulrike Faust, Roger L. Milne, Marta Santamariña, Lesley McGuffog, Jan Hauke, Christi J. van Asperen, Michela Raponi, Irene López-Perolio, Diana Baralle, Tina Pesaran, Huong Meeks, Peter J. Hulick, Miguel de la Hoya, Philip Whiley, Raquel Behar, Jenny Chang-Claude, Elizabeth C. Chao, Henrik Flyger, Doris Steinemann, Pham Phuong Mai, Stig E. Bojesen, Maaike P.G. Vreeswijk, Sandrine M. Caputo, Jan Sullivan, Julian Peto, Barbara Burwinkel, Laura Galastri, Per Hall, Kyriaki Michailidou, Bernd Dworniczak, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Fundación Pública Galega Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica--USC, CIBER de Enfermedades Raras (CIBERER), Division of Genetics and Population Health, Queensland Institute of Medical Research, Genetics, University of Southampton, University of Otago [Dunedin, Nouvelle-Zélande], Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, Human Genetics Division [Southampton], Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Institut Laue-Langevin (ILL), University of Melbourne, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, Institute of Cell and Molecular Pathology, Medizinische Hochschule Hannover (MHH), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), DIEP/DSV (DIEP/DSV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Ambry Genetics [Aliso Viejo, CA, USA], Department of Clinical Genetics, Royal Devon & Exeter Hospital, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Metabolic Unit, Dept Clinical Chemistry, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), Molecular Epidemiology Research Group, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Breast Surgery, Herlev and Gentofte Hospital, Karolinska University Hospital [Stockholm], Division of Cancer Epidemiology, Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medici, Cancer Epidemiology Centre, Cancer Council Victoria, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Ontario Cancer Genetics Network, Cancer Care Ontario, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Science and Technology Beijing [Beijing] (USTB), Strangeways Research Laboratory, University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Cancer Research U.K. Genetic Epidemiology Unit, Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Center for Human and Clinical Genetics, Université de Pau et des Pays de l'Adour (UPPA), International Agency for Cancer Research (IACR), ILL, Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Antoniou, Antonis [0000-0001-9223-3116], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Adult, RNA Splicing, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Breast Neoplasms, Biology, 03 medical and health sciences, Exon, Genetics, Humans, Allele, Molecular Biology, Gene, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Aged, Ovarian Neoplasms, Messenger RNA, BRCA1 Protein, Tumor Suppressor Proteins, Alternative splicing, RNA, General Medicine, Articles, Exons, Middle Aged, Splicing regulatory element, 3. Good health, Gene Expression Regulation, Neoplastic, Alternative Splicing, 030104 developmental biology, RNA splicing, Mutation, Female, RNA Splice Sites
Abstract: A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A>C (IVS9-2A>C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA and BCAC consortia to assess pathogenicity of c.594-2A>C. The combined odds for causality considering case-control, segregation, and breast tumor pathology information was 3.23x10-8. Our data indicate that c.594-2A>C is always in cis with c.641A>G.The spliceogenic effect of c.[594-2A>C;641A>G] was characterized using RNA analysis of human samples and splicing minigenes. As expected, c.[594-2A>C; 641A>G] caused exon 10 skipping, albeit not due to c.594-2A>C impairing the acceptor site but rather by c.641A>G modifying exon 10 splicing regulatory element(s). Multiple blood-based RNA assays indicated that the variant allele did not produce detectable levels of full-length transcripts, with a per allele BRCA1 expression profile comprised of ?70-80% truncating transcripts, and ?20-30% of in-frame ?9,10 transcripts predicted to encode a BRCA1 protein with tumor suppression function.We confirm that BRCA1c.[594-2A>C;641A>G] should not be considered a high-risk pathogenic variant. Importantly, results from our detailed mRNA analysis suggest that BRCA-associated cancer risk is likely not markedly increased for individuals who carry a truncating variant in BRCA1 exons 9 or 10, or any other BRCA1 allele that permits 20-30% of tumor suppressor function. More generally, our findings highlight the importance of assessing naturally occurring alternative splicing for clinical evaluation of variants in disease-causing genes.
Published: 2016

45. A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

Author: Travis, Ruth, Appleby, Paul, Martin, Richard, Holly, Jeff M.P., Albanes, Demetrius, Black, Amanda, Bueno-De-Mesquita, H. Bas, Chan, June, Chen, Chu, Chirlaque, María-Dolores, Cook, Michael, Deschasaux, Mélanie, Donovan, Jenny, Ferrucci, Luigi, Galan, Pilar, Giles, Graham, Giovannucci, Edward, Gunter, Marc, Habel, Laurel, Hamdy, Freddie, Helzlsouer, Kathy, Hercberg, Serge, Hoover, Robert, Janssen, Joseph A.M.J.L., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loïc, Metter, E. Jeffrey, Mikami, Kazuya, Morris, Joan, Neal, David, Neuhouser, Marian, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth, Pollak, Michael, Price, Alison, Roobol, Monique, Schaefer, Catherine, Schenk, Jeannette, Severi, Gianluca, Stampfer, Meir, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine, Touvier, Mathilde, Wald, Nicholas, Weiss, Noel, Ziegler, Regina, Key, Timothy, Allen, Naomi, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute on Aging [Bethesda, USA] (NIA), University of Melbourne, Harvard School of Public Health, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Kaiser Permanente, Nuffield (Nuffield), Mercy Medical Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Occupational and Environmental Health [Kitakyushu] (UEOH), University of Hawai‘i [Mānoa] (UHM), Kyoto Prefectural University of Medicine [Kyoto, Japon], Queen Mary University of London (QMUL), University of Cambridge [UK] (CAM), Radiation Effects Research Foundation, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Cancer Prevention Research Unit, Department of Oncology, McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, University of Washington [Seattle], Cancer Epidemiology Centre, Cancer Council Victoria, Human Genetics Foundation (HuGeF), Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Hokkaido University Hospital [Sapporo], University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Deschasaux-Tanguy, Mélanie
Subjects: Urologic Diseases, Male, Aging, Oncology and Carcinogenesis, Article, growth-factor-i, serum-insulin, Risk Factors, prevention trial, Humans, Oncology & Carcinogenesis, Insulin-Like Growth Factor I, factor axis, igfbp-3, Cancer, Aged, Prostate Cancer, hyperplasia, Prostatic Neoplasms, Middle Aged, susceptibility loci, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, factor-binding protein-2, Centre for Surgical Research, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, factor (igf)-i, diet, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. Aftermutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.
Published: 2016

46. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Author: Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J., Li, Qiyuan, Delgado, Melissa K., Lee, Janet M., Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Bandera, Elisa V., Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Børresen-Dale, Anne Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji Yeob, Claes, Kathleen B M, Cook, Linda S., Cox, Angela, Cramer, Daniel W., Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, Engel, Christoph, Lee, Eunjung, Evans, D. Gareth, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fridley, Brooke L., Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A., Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G., Glasspool, Rosalind, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Goode, Ellen L., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Heitz, Florian, Herzog, Josef, Høgdall, Estrid, Høgdall, Claus K., Hogervorst, Frans B L, Hollestelle, Antoinette, Hopper, John L., Hulick, Peter J., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jensen, Allan, John, Esther M., Johnson, Nichola, Kabisch, Maria, Kang, Daehee, Kapuscinski, Miroslav, Karlan, Beth Y., Khan, Sofia, Kiemeney, Lambertus A., Kjaer, Susanne Kruger, Knight, Julia A., Konstantopoulou, Irene, Kosma, Veli Matti, Kristensen, Vessela, Kupryjanczyk, Jolanta, Kwong, Ava, De La Hoya, Miguel, Laitman, Yael, Lambrechts, Diether, Le, Nhu, De Leeneer, Kim, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Lindblom, Annika, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lu, Karen, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Le Marchand, Loic, Margolin, Sara, Marme, Frederik, Massuger, Leon F A G, Matsuo, Keitaro, Mazoyer, Sylvie, McGuffog, Lesley, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Milne, Roger L., Montagna, Marco, Moysich, Kirsten B., Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Nord, Silje, Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olswold, Curtis, O'Malley, David, Orlow, Irene, Orr, Nick, Osorio, Ana, Park, Sue Kyung, Pearce, Celeste L., Pejovic, Tanja, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Poole, Elizabeth M., Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Rhenius, Valerie, Rhiem, Kerstin, Risch, Harvey A., Rodriguez, Gus, Rossing, Mary Anne, Rudolph, Anja, Salvesen, Helga B., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Sellers, Thomas A., Seynaeve, Caroline, Shah, Mitul, Shen, Chen Yang, Shu, Xiao Ou, Sieh, Weiva, Singer, Christian F., Sinilnikova, Olga M., Slager, Susan, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, Toland, Amanda Ewart, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tseng, Chiu Chen, Tung, Nadine, Tworoger, Shelley S., Vachon, Celine, Van Den Ouweland, Ans M W, Van Doorn, Helena C., Van Rensburg, Elizabeth J., Van't Veer, Laura J., Vanderstichele, Adriaan, Vergote, Ignace, Vijai, Joseph, Wang, Qin, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wu, Anna H., Yannoukakos, Drakoulis, Yoon, Sook Yee, Yu, Jyh Cherng, Zheng, Wei, Zheng, Ying, Khanna, Kum Kum, Simard, Jacques, Monteiro, Alvaro N., French, Juliet D., Couch, Fergus J., Freedman, Matthew L., Easton, Douglas F., Dunning, Alison M., Pharoah, Paul D., Edwards, Stacey L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Gayther, Simon A., Bowtell, David, DeFazio, Anna, Webb, Penny, Collonge-Rame, Marie Agnès, Damette, Alexandre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Ferrer, Sandra Fert, Bignon, Yves Jean, Uhrhammer, Nancy, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Adenis, Claude, Vénat-Bouvet, Laurence, Léone, Mélanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Verny-Pierre, Carole, Lasset, Christine, Bonadona, Valérie, Barjhoux, Laure, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Sokolowska, Johanna, Bronner, Myriam, Delnatte, Capucine, Bézieau, Stéphane, Mari, Véronique, Gauthier-Villars, Marion, Buecher, Bruno, Rouleau, Etienne, Golmard, Lisa, Moncoutier, Virginie, Belotti, Muriel, De Pauw, Antoine, Elan, Camille, Fourme, Emmanuelle, Birot, Anne Marie, Saule, Claire, Laurent, Maïté, Houdayer, Claude, Lesueur, Fabienne, Mebirouk, Noura, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Muller, Danièle, Fricker, Jean Pierre, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Mortemousque, Isabelle, Bressac-De-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brady, Angela, Barwell, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Cook, Jackie, Snape, Katie, Murray, Alex, McCann, Emma, Rookus, M. A., Van Leeuwen, F. E., Van Der Kolk, L. E., Schmidt, M. K., Russell, N. S., De Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., Van Deurzen, C. H M, Obdeijn, I. M., Van Asperen, C. J., Tollenaar, R. A E M, Van Cronenburg, T. C T E F, Kets, C. M., Ausems, M. G E M, Van Der Pol, C. C., Van Os, T. A M, Waisfisz, Q., Meijers-Heijboer, H. E J, Gómez-Garcia, E. B., Oosterwijk, J. C., Mourits, M. J., De Bock, G. H., Vasen, H. F., Siesling, S., Verloop, J., Overbeek, L. I H, Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Price, Melanie, NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Breast Cancer Research Trust, Instituto de Salud Carlos III, Lon V. Smith Foundation, Federal Ministry of Education & Research (Alemania), Finlands Akademi (Finlandia), United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Canadian Institutes of Health Research, Ministère de Économie, Innovation et Exportation (Canadá), Ministry of Higher Education (Malasia), National Medical Research Council (Singapur), University of Oulu (Finlandia), Yorkshire Cancer Research, Hellenic Cooperative Oncology Group, California Cancer Research Program, Danish Cancer Society, Ministry of Science and Higher Education (Polonia), Asociación Española Contra el Cáncer, University of Kansas. Cancer Center (Estados Unidos), Hungarian Research Grants, Norwegian EEA Financial Mechanism, Canadian Breast Cancer Network, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Congressionally Directed Medical Research Programs (Estados Unidos), NRG Oncology National (Estados Unidos), Unión Europea. 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Petrov Institute of Oncology, St Petersburg 197758, Russia. 125 Lombardi Comprehensive Cancer Center, Georgetown University, Washington District of Columbia 20057, USA. 126 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi 464-8681, Japan. 127 State Research Institute Centre for Innovative Medicine, LT-01102 Vilnius, Lithuania. 128 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA. 129 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 08826, Korea. 130 Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia. 131Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 132 Radboud University Medical Centre, Radboud Institute for Health Sciences, 6500 Nijmegen, The Netherlands. 133 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. 134 Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. 135 Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, 70210 Kuopio, Finland. 136 Cancer Center, Kuopio University Hospital, 70210 Kuopio, Finland. 137 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland. 138 Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, 1478 Oslo, Norway. 139 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. 140 Department of Surgery, The University of Hong Kong, Hong Kong, China. 141Vesalius Research Center, VIB, 3000 Leuven, Belgium. 142 Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. 143 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 144 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK. 145 Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 146 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), 20133 Milan, Italy. 147 University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. 148 Department of Oncology - Pathology, Karolinska Institutet, SE- 171 77 Stockholm, Sweden. 149 National Center for Tumour Diseases, University of Heidelberg, 69117 Heidelberg, Germany. 150 Department of Gynaecology, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 151 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka 812-8582, Japan. 152 Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria 3004, Australia. 153 Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. 154 Division of Gynaecology and Obstetrics, Technische Universita¨t Mu¨nchen, 81675 Munich, Germany. 155 Department of Human Genetics, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 156 Immunology and Molecular Oncology Unit, Instituto Oncologico Veneto IOV, IRCCS, 35128 Padua, Italy. 157 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 158 Institute of Population Health, University of Manchester, Manchester M13 9PL, UK. 159 Laboratory Medicine Program, University Health Network, Toronto, Ontario M5G 1L7, Canada. 160 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada. 161 The University of Texas School of Public Health, Houston, Texas 77030, USA. 162 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA. 163 Department of Medicine and Genetics, University of California, San Francisco, California 94143, USA. 164 Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 165 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 166 Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary. 167 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA. 168 The Ohio State University and the James Cancer Center, Columbus, Ohio 43210, USA. 169 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York 10017, USA. 170 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28019 Madrid, Spain. 171 Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain. 172 Department of Surgery, Seoul National University College of Medicine, Seoul, 03080 Korea. 173 Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. 174 Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. 175 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, 16 20139 Milan, Italy. 176 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. 177 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida 33606, USA. 178 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 179 Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts 02115, USA. 180 Laboratory of Cancer Genetics and Tumour Biology, Northern Finland Laboratory Centre NordLab, FI-90014 Oulu, Finland. 181 Laboratory of Cancer Genetics and Tumour Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland. 182 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT),cine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA. 2 Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 3 QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia. 4 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 5 Medical College, Xiamen University, Xiamen 361102, China. 6 Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 7 Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki 00029 HUS, Finland. 8 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario Canada, M5G 1X5. 9 Department of Molecular Genetics, University of Toronto, Toronto, OntarioCanada, M5S 1A8. 10 Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California 92697, USA. 11 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany. 12 University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 13 Department of Oncology, Karolinska University Hospital, Stockholm 171 77, Sweden. 14 Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA. 15 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan 20141, Italy. 16 Department of Pathology, Landspitali University Hospital and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik 600169- 2039, Iceland. 17 University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen 91054, Germany. 18 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid E-28029, Spain. 19 Centro de Investigacio´n en Red de Enfermedades Raras, Valencia 28029, Spain. 20 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710, USA. 21 Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 22 Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway. 23 Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway. 24 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland. 25 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. 26 International Epidemiology Institute, Rockville, Maryland 20850, USA. 27 Gynaecology Research Unit, Hannover Medical School, Hannover D-30625, Germany. 28 Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark. 29 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. 30 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 31 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 32 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo N-0310, Norway. 33 K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo N-0310, Norway. 34 Dr Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart D-70376, Germany. 35 University of Tu¨bingen, Tu¨bingen 72074, Germany. 36 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 37 International Agency for Research on Cancer, Lyon 69008, France. 38 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 39 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. 40 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d’Investigacio´ Biome`dica de Girona), Catalan Institute of Oncology, Girona 08908, Spain. 41 Department of Surgery, National University Health System, Singapore 119077, Singapore. 42 Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 43 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg 69120, Germany. 44 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00029 HUS, Finland. 45 Department of Pathology, Helsinki University Central Hospital, Helsinki 00029, Finland. 46 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. 47 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigacio´n Sanitaria del Hospital Clı ´nico San Carlos), Madrid 28040, Spain. 48 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia. 49 Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo 14263, New York, USA. 50 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 51 University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany. 52 Unite´ de recherche en sante´ des populations, Centre des maladies du sein Descheˆnes-Fabia, Centre de recherche FRSQ du Centre hospitalier affilie´ universitaire de Que´bec, Que´bec City, Que´bec Canada, G1J 1Z4. 53 Cancer Research Institute, Seoul National University, Seoul 08826, Korea. 54 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. 55 Center for Medical Genetics, Ghent University, Ghent 9000, Belgium. 56 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA. 57 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield S10 2TN, UK. 58 Harvard HT Chan School of Public Health, Boston, Massachusetts 02115, USA. 59 Obstetrics and Gynecology Epidemiology Center, Brigham andWomen’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 60 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK. 61 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-115, Poland. 62 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-171 77, Sweden. 63 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 64 INSERM U1052, CNRS UMR5286, Universite´ Lyon, Centre de Recherche en Cance´rologie de Lyon, Lyon 69373, France. 65 Department of Pathology and Laboratory Diagnostics the Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology,Warsaw 44-101, Poland. 66 Department of Pathology, Leiden University Medical Center, Leiden 2333, The Netherlands. 67 Department of Human Genetics, Leiden University Medical Center, Leiden 2333, The Netherlands. 68 Oncogenetics Group, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO) and Universitat Auto`noma de Barcelona, Barcelona, 186 Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, 50931 Cologne, Germany. 187Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut 06510, USA. 188Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois 60201, USA. 189 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. 190Department of Epidemiology, University of Washington, Seattle, Washington 98109, USA. 191National Cancer Institute, Bangkok 10400, Thailand. 192 Research Oncology, Guy’s Hospital, King’s College London, London SE1 9RT, UK. 193Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. 194 Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina 27710, USA. 195Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands. 196Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, 50676 Cologne, Germany. 197 Center for Integrated Oncology, University Hospital of Cologne, 50676 Cologne, Germany. 198 Center for Molecular Medicine, University Hospital of Cologne, 50676 Cologne, Germany. 199 Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, 50676 Cologne, Germany. 200 Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. 201 School of Public Health, China Medical University, Taichung 404, Taiwan. 202Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford California 94305, USA. 203 Unite´ Mixte de Ge´ne´tique Constitutionnelle des Cancers Fre´quents, Hospices Civils de Lyon – Centre Le´on Be´rard, Lyon 69008, France. 204 INSERM U1052, CNRS UMR5286, Universite´ Lyon 1, Centre de Recherche en Cance´rologie de Lyon, Lyon 69003, France. 205Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia. 206Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linko¨ping University, 581 83 Linko¨ping, Sweden. 207 Institut Curie, Department of Tumour Biology, Paris, France, Institut Curie, INSERM U830, 75248 Paris, France. 208Universite´ Paris Descartes, Sorbonne Paris Cite´, 75270 Paris, France. 209 Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany. 210Department of Genetics, Portuguese Oncology Institute, Porto 4200-072, Portugal. 211 Biomedical Sciences Institute (ICBAS), Porto University, Porto 4099-002, Portugal. 212Department of Epidemiology, Mailman School of Public Health, Columbia University, New York 10027, USA. 213Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark. 214UO Anatomia Patologica, Ospedale di Circolo-Universita` dell’Insubria, 21100 Varese, Italy. 215 Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia. 216 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), 64 - 35128 Padua, Italy. 217Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA. 218Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK. 219 Institute of Human Genetics, Pontificia Universidad Javeriana, Cra. 7 #40-62 Bogota, Colombia. 220Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 221Department of Clinical Genetics, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands. 222Department of Gynecology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands. 223Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 224University Hospital Ulm, 89069 Ulm, Germany. 225Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Maryland 20892, USA. 226 Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 227 Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, Athens 153 10, Greece. 228 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 47500 Subang Jaya, Malaysia. 229 University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Malaysia. 230Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114 Taiwan. 231 Shanghai Center for Disease Control and Prevention, Shanghai, China. 232 Cancer Epidemiology Program, Division of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. 233Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. 234 Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. 235 Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. 236 Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK. 237 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia. 238 Department of Gynaecological Oncology, Westmead Institute for Cancer Research, Westmead Hospital Westmead, New South Wales 2145, Australia., Tyrer, Jonathan [0000-0003-3724-4757], Dennis, Joe [0000-0003-4591-1214], Rhenius, Valerie [0000-0003-4215-3235], Song, Honglin [0000-0001-5076-7371], Wang, Jean [0000-0002-9139-0627], Easton, Douglas [0000-0003-2444-3247], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Quality of care, Anesthesiology, Human genetics, CCA - Cancer biology, and VU University medical center
Subjects: endocrine system diseases, Messenger, IDENTIFIES 3, MODIFIERS, Brjóstakrabbamein, BRCA2 MUTATION CARRIERS, Medicine and Health Sciences, GWAS, INVESTIGATORS, African Continental Ancestry Group, Asian Continental Ancestry Group, Breast Neoplasms, Chromosomes, Human, Pair 19, Female, Genome-Wide Association Study, Genotype, Humans, Ovarian Neoplasms, RNA, Messenger, Alleles, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, skin and connective tissue diseases, COMMON VARIANTS, EPITHELIAL-CELLS, Single Nucleotide, female genital diseases and pregnancy complications, NAF12, Medical Genetics, Human, endocrine system, Science, Chromosomes, Human, Pair 19/genetics, Black People, Breast Neoplasms/genetics, Chromosomes, Article, Ovarian Neoplasms/genetics, SDG 3 - Good Health and Well-being, Asian People, REVEALS, Polymorphism, GENOME-WIDE ASSOCIATION, Krabbamein, Medicinsk genetik, Cancer och onkologi, Pair 19, Arfgengi, GENE, Eggjastokkar, Cancer and Oncology, RNA, BRCA1 Protein/genetics
Abstract: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P, A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.
Published: 2016

47. Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Author: Sabina Rinaldi, Aurelio Barricarte, Dimitrios Trichopoulos, Evelyn M. Monninkhof, Françoise Clavel-Chapelon, Anne Tjønneland, Amalia Mattiello, Laure Dossus, Renée T. Fortner, Virginia Menéndez, Vittorio Krogh, Kim Overvad, Fulvio Ricceri, Antonia Trichopoulou, Rosario Tumino, Laura Baglietto, Kaja Tikk, Elisabete Weiderpass, Disorn Sookthai, Ruth C. Travis, Timothy J. Key, María José Sánchez, Antonio Agudo, Giovanna Masala, Isabelle Romieu, Elio Riboli, Heiner Boeing, María Dolores Chirlaque, Malin Sund, Theron Johnson, Anja Olsen, N. Charlotte Onland-Moret, Anne Andresson, Rudolf Kaaks, Hbas Bueno-de-Mesquita, Pagona Lagiou, Pilar Amiano, Kay-Tee Khaw, Melissa A. Merritt, [Tikk,K, Sookthai,D, Fortner,RT, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Rinaldi,S, Romieu,I] Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. [Tjønneland,D, Olsen,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Dossus,l] INSERM, Centre for Research in Epidemiology and Population Health [CESP], Nutrition, Hormones and Women’s Health team, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] Univ Paris Sud, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] IGR, Villejuif, France. [Baglietto,L] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Australia. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece.[Trichopoulou,A, Lagiou.P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P.Arezzo' Hospital ASP, Ricceri, Ragusa, Italy. [Ricceri,F] Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Sánchez,M] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitario de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Reserach Institute, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Sánchez, M, Amiano, P, Chirlaque,M, Barricarte,A] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiología y Salud Pública (CIBERESP)), Madrid, Spain. [Bueno-de-Mesquita,H] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,H, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College, London, UK. [Monninkhof,EM, Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Andresson,A] Department of Radiation Sciences, University of Umeå, Umeå, Sweden. [Sund,M] Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland, [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, UK. [Key,TJ, and Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tikk,K] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
Subjects: Oncology, Cancer Research, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Gonadotropins::Gonadotropins, Pituitary::Prolactin [Medical Subject Headings], PERIOD, Prolactina, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Risk Factors, REPRODUCIBILITY, HISTORY, Odds Ratio, 0303 health sciences, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Neoplasias de la Mama, Estudios de Casos y Controles, Middle Aged, Adult, Aged, Breast Neoplasms, Carcinoma in Situ, Case-Control Studies, Europe, Female, Follow-Up Studies, Humans, Logistic Models, Menopause, Prolactin, 3. Good health, European Prospective Investigation into Cancer and Nutrition, POSTMENOPAUSAL WOMEN, PREMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Cohort, Life Sciences & Biomedicine, Cohort study, Research Article, medicine.medical_specialty, CARCINOMA, STEROID-HORMONES, Riesgo, Càncer de mama, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, Journal Article, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Cancer och onkologi, Science & Technology, business.industry, Carcinoma in situ, Case-control study, Odds ratio, medicine.disease, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ [Medical Subject Headings], Cancer and Oncology, PLASMA PROLACTIN, business
Abstract: Introduction The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), P-trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P-het = 0.98) or baseline HT use (P-het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P-trend = 0.06 vs P-trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors = 4 years after blood donation (P-trend = 0.01 vs P-trend = 0.63; P-het = 0.04) and among nulliparous women compared to parous women (P-trend = 0.03 vs P-trend = 0.15; P-het = 0.07). Conclusions Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.
Published: 2015

48. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies

Author: Ruth C. Travis, Demetrius Albanes, Pilar Galan, H. Bas Bueno-de-Mesquita, Judy Hoffman-Bolton, Aurelio Barricarte, Harri Rissanen, Satu Männistö, Markku Heliövaara, Rebecca Gilbert, Timothy J. Key, Jenny L Donovan, Gary E. Goodman, Naomi E. Allen, Mathilde Touvier, Robert N. Hoover, Cindy Ke Zhou, Richard M. Martin, Jeannette M. Schenk, Regina G. Ziegler, Graham G. Giles, Irena B. King, Haakon E. Meyer, June M. Chan, Michael B. Cook, Meir J. Stampfer, Camille Pouchieu, Phyllis J. Goodman, Loic Le Marchand, Gianluca Severi, Elizabeth A. Platz, Amanda Black, Stephanie J. Weinstein, Marc J. Gunter, Marian L. Neuhouser, Freddie C. Hamdy, Alison M. Mondul, Laurence N. Kolonel, Serge Hercberg, Antonia Trichopoulou, Mattias Johansson, Kay-Tee Khaw, Anne Tjønneland, Anthony J. Alberg, Paul Knekt, Kathy J. Helzlsouer, Heiner Boeing, David E. Neal, Brian E. Henderson, Kristin A. Moy, Chu Chen, Edward Giovannucci, Paul N. Appleby, Domenico Palli, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, The Netherlands Cancer Institute, Medical University of South Carolina [Charleston] (MUSC), Navarra Public Health Institute, Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), German Institute of Human Nutrition, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Centre, School of Public Health, Imperial College London, University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), School of Social and Community Medicine, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Epidemiology Centre, Cancer Council Victoria, Harvard School of Public Health, Brigham and Women's Hospital [Boston], University of Washington [Seattle], National Institute of Health and Welfare, Prevention and Research Center, Mercy Medical Center, University of Southern California (USC), Johns Hopkins Bloomberg School of Public Health, Partenaires INRAE, International Agency for Research on Cancer (IARC), Umeå University, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM)-Institute of Public Health, The University of New Mexico [Albuquerque], Cancer Center, Massachusetts General Hospital [Boston], Medical Research Council, National Institute for Health Research (NHS), University of Oslo (UiO), Norwegian institute for public health, Department of Oncology, University of Cambridge [UK] (CAM), Istituto per lo Studio e la Prevezione Oncologica, Cancer Prevention Program, Institute of Cancer Epidemiology, The Danish Cancer Society, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, ProdInra, Migration, University of Oxford, University of California [San Francisco] (UC San Francisco), and University of California (UC)
Subjects: Male, Oncology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], alpha-Tocopherol, Medicine (miscellaneous), Cohort Studies, chemistry.chemical_compound, Prostate cancer, Lycopene, Risk Factors, Prostate, Prospective Studies, Carotenoid, Cancer, chemistry.chemical_classification, Nutrition and Dietetics, Retinol, carotenoids, food and beverages, vitamin e, Middle Aged, prostate cancer, vitamin a, 3. Good health, [SDV] Life Sciences [q-bio], Observational Studies as Topic, medicine.anatomical_structure, pooled analysis, tocopherols, retinol, Adult, medicine.medical_specialty, Meta-Analysis as Topic, beta-Carotene, Internal medicine, medicine, Humans, Neoplasm Staging, nested case control study, business.industry, Vitamin E, Case-control study, Prostatic Neoplasms, biomarkers, medicine.disease, Cross-Sectional Studies, Endocrinology, chemistry, Case-Control Studies, Nested case-control study, Neoplasm Grading, business
Abstract: International audience; Background: Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. Objective: The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, alpha-tocopherol, and gamma-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors. Design: Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets. Results: Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For alpha-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). gamma-Tocopherol was not associated with risk. Conclusions: Overall prostate cancer risk was positively associated with retinol and inversely associated with alpha-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and alpha-tocopherol. Whether these associations reflect causal relations is unclear.
Published: 2015

49. Occupational exposure to extremely low-frequency magnetic fields and brain tumor risks in the INTEROCC study

Author: Daniel Krewski, Martie van Tongeren, Jack Siemiatycki, Laurel Kincl, Brigitte Schlehofer, Klaus Schlaefer, Jordi Figuerola, Michelle C. Turner, Martine Hours, David McLean, Geza Benke, Joseph D. Bowman, Elisabeth Cardis, Joachim Schüz, Siegal Sadetzki, Sarah Fleming Fleming, Marie-Élise Parent, Lesley Richardson, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), University of Ottawa [Ottawa], Monash University [Clayton], National Institute for Occupational Safety and Health, NIOSH, University of Leeds, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Oregon State University (OSU), Massey University, Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Université de Montréal (UdeM), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Cancer and Radiation Epidemiology Unit, The Gertner Institute for Epidemiology and Health Policy Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institute of Occupational Medicine [Edinburgh] (IOM), M.C. Turner was supported by a Government of Canada Banting Postdoctoral Fellowship. The INTEROCC study was supported by the NIH Grant No. 1R01CA124759 (PI E. Cardis). Coding of the French occupational data was in part was supported by AFSSET (Convention No. ST-2005-004). The INTERPHONE study was supported by funding from the European Fifth Framework Program, 'Quality of Life and Management of Living Resources' (contract 100 QLK4-CT-1999901563) and the International Union against Cancer (UICC). The UICC received funds for this purpose from the Mobile Manufacturers’ Forum and GSM Association. In Australia, funding was received from the Australian National Health and Medical Research 5 Council (EME Grant 219129) with funds originally derived from mobile phone service license fees, a University of Sydney Medical Foundation Program, the Cancer Council NSW and The Cancer Council Victoria. In Canada, funding was received from the Canadian Institutes of Health Research (project MOP-42525), the Canada Research Chair programme, the Guzzo-CRS Chair in Environment and Cancer, the Fonds de la recherche en santé du Québec, the Canadian Institutes of Health Research (CIHR), the latter including partial support from the Canadian Wireless Telecommunications Association, the NSERC Chair in Risk Science at the University of Ottawa. In France, funding was received by l’Association pour la Recherche sur le Cancer (ARC, Contract N85142) and 3 network operators (Orange, SFR, and Bouygues Telecom). In Germany, funding was received from the German Mobile Phone Research Program (Deutsches Mobilfunkforschungsprogramm) of the German Federal Ministry for the Environment, Nuclear 45 Safety, and Nature Protection, the Ministry for the Environment and Traffic of the state of Baden-Wurttemberg, the Ministry for the Environment of the state of North Rhine-Westphalia, the MAIFOR Program (Mainzer Forschungsforderungsprogramm) of the University of Mainz. In New Zealand, funding was provided by the Health Research Council, Hawkes Bay Medical Research Foundation, the Wellington Medical Research Foundation, the Waikato Medical Research Foundation, and the Cancer Society of New Zealand. Additional funding for the UK study was received from the Mobile Telecommunications, Health and Research (MTHR) program, funding from the Health and Safety Executive, the Department of Health, the UK Network Operators (O2, Orange, T-Mobile, Vodafone, and '3'), and the Scottish Executive., European Project: 1999901563,QLK4-CT, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), and Tel Aviv University (TAU)
Subjects: Adult, Male, Oncology, Canada, medicine.medical_specialty, Pathology, Percentile, Epidemiology, [SDV]Life Sciences [q-bio], Population, Job-exposure matrix, PROFESSION, Cumulative Exposure, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Germany, Occupational Exposure, Glioma, Internal medicine, CERVEAU, Humans, Medicine, Risk factor, education, Aged, FREQUENCE, education.field_of_study, Brain Neoplasms, business.industry, Australia, Odds ratio, Middle Aged, respiratory system, medicine.disease, 030210 environmental & occupational health, United Kingdom, Confidence interval, 3. Good health, CHAMP ELECTROMAGNETIQUE, Occupational Diseases, Magnetic Fields, 030220 oncology & carcinogenesis, Female, France, business
Abstract: Background: Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study. Methods: Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, and the United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix were assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1 to 4, 5 to 9, and 10+ years before the diagnosis/reference date. Results: There were 3,761 included brain tumor cases (1,939 glioma and 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1 to 4 years before the diagnosis/reference date and glioma [odds ratio (OR) ≥ 90th percentile vs. < 25th percentile, 1.67; 95% confidence interval (CI), 1.36–2.07; PLinear trend < 0.0001], and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs. < 25th percentile, 1.23; 95% CI, 0.97–1.57; PLinear trend = 0.02). Conclusions: Results showed positive associations between ELF in the recent past and glioma. Impact: Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumorigenesis. Cancer Epidemiol Biomarkers Prev; 23(9); 1863–72. ©2014 AACR.
Published: 2014

50. DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Osorio, Ana, Milne, Roger L., Kuchenbaecker, Karoline, Vaclová, Tereza, Pita, Guillermo, Alonso, Rosario, Peterlongo, Paolo, Blanco Guillermo, Ignacio, De la Hoya, Miguel, Durán, Mercedes, Diez, Orland, Ramon y Cajal, Teresa, Konstantopoulou, Irene, Martínez-Bouzas, Cristina, Andrés Conejero, Raquel, Soucy, Penny, McGuffog, Lesley, Barrowdale, Daniel, Lee, Andrew, SWE-BRCA, None, Arver, Brita, Rantala, Johanna, Loman, Niklas, Ehrencrona, Hans, Olopade, Olufunmilayo I., Beattie, Mary S., Domchek, Susan M., Nathanson, Katherine, Rebbeck, Timothy R., Arun, Banu K., Karlan, Beth Y., Walsh, Christine, Lester, Jenny, John, Esther M., Whittemore, Alice S., Daly, Mary B., Southey, Melissa, Hopper, John L, Terry, Mary Beth, Buys, Saundra, Janavicius, Ramunas, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Steele, Linda, Neuhausen, Susan L., Ding, Yuan Chun, Hansen, Thomas v. O., Jønson, Lars, Ejlertsen, Bent, Gerdes, Anne-Marie, Infante, Mar, Herráez, Belén, Moreno, Leticia Thais, Weitzel, Jeffrey N., Herzog, Josef, Weeman, Kisa, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Scuvera, Giulietta, Bonanni, Bernardo, Mariette, Frederique, Volorio, Sara, Viel, Alessandra, Varesco, Liliana, Papi, Laura, Ottini, Laura, Tibiletti, Maria Grazia, Radice, Paolo, Yannoukakos, Drakoulis, Garber, Judy, Ellis, Steve, Frost, Debra, Platte, Radka, Fineberg, Elena, Evans, Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Eccles, Diana M, Cook, Jackie, Hodgson, Shirley, Brewer, Carole, Tischkowitz, Marc, Douglas, Fiona, Porteous, Mary, Side, Lucy, Walker, Lisa, Morrison, Patrick, Donaldson, Alan, Kennedy, John, Foo, Claire, Godwin, Andrew K., Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hans Jörg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Gehrig, Andrea, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M., Mazoyer, Sylvie, Damiola, Francesca, Poppe, Bruce, Claes, Kathleen, Piedmonte, Marion, Tucker, Kathy, Backes, Floor, Rodríguez, Gustavo, Brewster, Wendy, Wakeley, Katie, Rutherford, Thomas, Caldes, Trinidad, Nevanlinna, Heli, Aittomäki, Kristiina, Rookus, Matti A., van Os, Theo A. M., van der Kolk, Lizet, de Lange, J. L., Meijers-Heijboer, Hanne E. J., van der Hout, A. H., van Asperen, Christi J., Gómez Garcia, Encarna B., Hoogerbrugge, Nicoline, Collée, J. Margriet, van Deurzen, Carolien H. M., van der Luijt, Rob B., Devilee, Peter, HEBON, None, Olah, Edith, Lázaro, Conxi, Teulé, Alex, Menéndez, Mireia, Jakubowska, Anna, Cybulski, Cezary, Gronwald, Jacek, Lubinski, Jan, Durda, Katarzyna, Jaworska-Bieniek, Katarzyna, Johannsson, Oskar Th., Maugard, Christine, Montagna, Marco, Tognazzo, Silvia, Teixeira, Manuel R., Healey, Sue, Investigators, kConFab, Olswold, Curtis, Guidugli, Lucia, Lindor, Noralane, Slager, Susan, Szabo, Csilla I., Vijai, Joseph, Robson, Mark, Kauff, Noah, Zhang, Liying, Rau-Murthy, Rohini, Fink-Retter, Anneliese, Singer, Christian F., Rappaport, Christine, Geschwantler Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Berger, Andreas, Phelan, Catherine M., Greene, Mark H., Mai, Phuong L., Lejbkowicz, Flavio, Andrulis, Irene L., Mulligan, Anna Marie, Glendon, Gord, Toland, Amanda Ewart, Bojesen, Anders, Pedersen, Inge Sokilde, Sunde, Lone, Thomassen, Mads, Kruse, Torben A., Jensen, Uffe Birk, Friedman, Eitan, Laitman, Yael, Shimon, Shani Paluch, Simard, Jacques, Easton, Douglas F., Offit, Kenneth, Couch, Fergus J., Chenevix-Trench, Georgia, Antoniou, Antonis C., Benitez, Javier, Universitat Autònoma de Barcelona, Pediatric Surgery, Clinical Genetics, Pathology, Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain, Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. 2Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 4Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. 5Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain. 6IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. 7Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 8Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain. 9Institute of 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Cedars-Sinai Medical Center, Los Angeles, California, United States of America. 27Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California, United States of America. 28Department of Health Research & Policy, Stanford University School of Medicine, Stanford, California, United States of America. 29Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America. 30Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Australia. 31Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia. 32Department of Epidemiology, Columbia University, New York, New York, United States of America. 33Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, United States of America. 34Vilnius University Hospital Santariskiu Clinics, Hematology, oncology and transfusion medicine center, Department of Molecular and Regenerative Medicine, Vilnius, Lithuania. 35Department of Genetics, University of Pretoria, Pretoria, South Africa. 36Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America. 37Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 38Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 39Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 40Clinical Cancer Genetics, City of Hope, Duarte, California, United States of America. 41Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy. 42Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy. 43IFOM, Fondazione Istituto FIRC di Oncologia Molecolare and Cogentech Cancer Genetic Test Laboratory, Milan, Italy. 44Division of Experimental Oncology 1, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy. 45Unit of Hereditary Cancer, Department of Epidemiology, Prevention and Special Functions, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 46Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy. 47Department of Molecular Medicine, 'Sapienza' University, Rome, Italy. 48UO Anatomia Patologica, Ospedale di Circolo-Università dell'Insubria, Varese, Italy. 49Unit of Molecular bases of genetic risk and genetic testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy. 50Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America. 51Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom. 52South East Thames Regional Genetics Service, Guy's Hospital London, United Kingdom. 53Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, United Kingdom. 54Yorkshire Regional Genetics Service, Leeds, United Kingdom. 55Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, United Kingdom. 56West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, United Kingdom. 57Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, United Kingdom. 58Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom. 59Clinical Genetics Department, St Georges Hospital, University of London, London, United Kingdom. 60Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, United Kingdom. 61Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, United Kingdom. 62Institute of Human Genetics, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom. 63South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, United Kingdom. 64North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom. 65Oxford Regional Genetics Service, Churchill Hospital, Oxford, United Kingdom. 66Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, United Kingdom. 67South West Regional Genetics Service, Bristol, United Kingdom. 68Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin and St James's Hospital, Dublin, Eire. 69Cheshire & Merseyside Clinical Genetics Service, Liverpool Women's NHS Foundation Trust, Liverpool, United Kingdom. 70Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America. 71Centre of Familial Breast and Ovarian Cancer and Centre for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany. 72Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. 73Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. 74Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. 75Institute of Human Genetics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. 76Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. 77Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany. 78Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany. 79Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany. 80Institute of Human Genetics, University of Münster, Münster, Germany. 81Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. 82Institute of Human Genetics, Campus Virchov Klinikum, Charite Berlin, Berlin, Germany. 83Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University Würzburg, Würzburg, Germany. 84Institut Curie, Department of Tumour Biology, Paris, France, Institut Curie, INSERM U830, Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 85Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon - Centre Léon Bérard, Lyon, France, INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. 86INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. 87Center for Medical Genetics, Ghent University, Ghent, Belgium. 88Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York, United States of America. 89Prince of Wales Hospital. Sydney, Australia. 90Ohio State University, Columbus Cancer Council, Columbus, Ohio, United States of America. 91Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois, United States of America. 92Division of Gynecologic Oncology, NorthShore University HealthSystem, Chicago, Illinois, United States of America. 93For Tufts Medical Center, Boston, Massachusetts, United States of America. 94Yale University School of Medicine, New Haven, Connecticut, United States of America. 95Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. 96Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 97Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. 98Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands. 99Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands. 100University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands. 101Department of Clinical Genetics, Leiden University Medical Center Leiden, Leiden, The Netherlands. 102Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, MUMC, Maastricht, The Netherlands. 103Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 104Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands. 105Department of Pathology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands. 106Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. 107Department of Human Genetics & Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. 108The Hereditary Breast and Ovarian Cancer Research Group, Netherlands Cancer Institute, Amsterdam, The Netherlands. 109Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. 110Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. 111Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. 112Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland. 113Department of Oncology, Landspitali University Hospital and BMC, Faculty of Medicine, University of Iceland, Reykjavik Iceland. 114Laboratoire de Diagnostic Génétique et Service d'Onco-hématologie, Hopitaux Universitaire de Strasbourg, CHRU Nouvel Hôpital Civil, Strasbourg, France. 115Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy. 116Department of Genetics, Portuguese Oncology Institute, Porto, and Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal. 117Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, Australia. 118Kathleen Cuningham Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Center, Melbourne, Australia. 119Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America. 120Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America. 121Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, United States of America. 122Center for Translational Cancer Research, Department of Biological Sciences, University of Delaware, Newark, Delaware, United States of America. 123Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. 124Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. 125Diagnostic Molecular Genetics Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. 126Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 127Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America. 128Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, United States of America. 129Clalit National Israeli Cancer Control Center, Haifa, Israel. 130Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, and Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. 131Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada. 132Ontario Cancer Genetics Network: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. 133Division of Human Cancer Genetics, Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America. 134Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark. 135Section of Molecular Diagnostics, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark. 136Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. 137Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. 138Sheba Medical Center, Tel Aviv, Israel. 139Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Canada. 140Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America. 141Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain, Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain, Genotyping Unit (CeGen), Spanish National Cancer Centre (CNIO), Madrid, Spain., SWE-BRCA, Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Unión Europea, Cancer Research UK (Reino Unido), United States of Department of Health & Human Services, Canadian Institutes of Health Research, Susan G. Komen Breast Cancer Foundation, Ralph and Marion Falk Medical Research Trust, Research Council (Lituania), University of Kansas. Cancer Center (Estados Unidos), National Institute for Health Research (Reino Unido), Deutsche Krebshilfe, Finlands Akademi (Finlandia), Dutch Cancer Society (Holanda), Dutch Research Council (Holanda), Pink Ribbons Project, Hungarian Scientific Research Fund (Hungría), Canadian Breast Cancer Network, Ministère du Développement économique, de Innovation et de Exportation (Canadá), Westat (Estados Unidos), Department of Obstetrics and Gynecology, Clinicum, Universitat de Barcelona, Human Genetics, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Lee, Andrew [0000-0003-0677-0252], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Human genetics, CCA - Oncogenesis, Fundación Mutua Madrileña Automovilista, Fundacion Asociacion Espanola Contra el Cancer (AECC), Instituto de Salud Carlos III - ISCIII, European Union (EU), Cancer Research UK, United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Canadian Institutes of Health Research (CIHR), Research Council of Lithuania, University of Kansas Cancer Center, National Institute for Health Research (NIHR), Academy of Finland, KWF Kankerbestrijding, Netherlands Organization for Scientific Research (NWO), Pink Ribbon grant, Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA), Canadian Breast Cancer Research Alliance-grant, Ministry of Economic Development, Innovation and Export Trade, and Westat, Inc, Rockville, MD
Subjects: Cancer Research, 24 Ciencias de la Vida, DNA Repair, endocrine system diseases, ADN, Càncer d'ovari, Synthetic lethality, BRCA1 Protein/genetics, DNA Glycosylases, 0302 clinical medicine, DNA Glycosylases/genetics, Brjóstakrabbamein, Genotype, Medicine and Health Sciences, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Glicosilasas, INVESTIGATORS, skin and connective tissue diseases, OGG1, Genetics (clinical), Genetics, DAMAGE, Aged, 80 and over, Ovarian Neoplasms, 0303 health sciences, BRCA1 Protein, SINGLE-NUCLEOTIDE POLYMORPHISMS, COMMON VARIANTS, Base excision repair, Middle Aged, BRCA2 Protein, 3. Good health, 030220 oncology & carcinogenesis, NEIL2, Female, Medical Genetics, Research Article, BRCA1, BRCA2, Adult, Risk, Ovarian Neoplasms/genetics, lcsh:QH426-470, Adolescent, DNA repair, education, Single-nucleotide polymorphism, Breast Neoplasms, DNA Repair/genetics, Biology, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, OVARIAN-CANCER, 03 medical and health sciences, Polymorphism, Single Nucleotide/genetics, SDG 3 - Good Health and Well-being, Ovarian cancer, Cancer Genetics, BREAST-CANCER, Humans, Genetic Predisposition to Disease, ddc:610, Molecular Biology, Gene, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Aged, BRCA2 Protein/genetics, CONSORTIUM, Biology and Life Sciences, Arfgengi, lcsh:Genetics, DNA glycosylase, Cancer research, 3111 Biomedicine, GENETIC MODIFIERS, Genètica
Abstract: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p, Author Summary Women harboring a germ-line mutation in the BRCA1 or BRCA2 genes have a high lifetime risk to develop breast and/or ovarian cancer. However, not all carriers develop cancer and high variability exists regarding age of onset of the disease and type of tumor. One of the causes of this variability lies in other genetic factors that modulate the phenotype, the so-called modifier genes. Identification of these genes might have important implications for risk assessment and decision making regarding prevention of the disease. Given that BRCA1 and BRCA2 participate in the repair of DNA double strand breaks, here we have investigated whether variations, Single Nucleotide Polymorphisms (SNPs), in genes participating in other DNA repair pathway may be associated with cancer risk in BRCA carriers. We have selected the Base Excision Repair pathway because BRCA defective cells are extremely sensitive to the inhibition of one of its components, PARP1. Thanks to a large international collaborative effort, we have been able to identify at least two SNPs that are associated with increased cancer risk in BRCA1 and BRCA2 mutation carriers respectively. These findings could have implications not only for risk assessment, but also for treatment of BRCA1/2 mutation carriers with PARP inhibitors.
Published: 2014

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