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1. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.

Author: Spurdle, Amanda B, Couch, Fergus J, Parsons, Michael T, McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K, Wang, Qin, Healey, Sue, Schmutzler, Rita, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L, Domchek, Susan M, Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Åke, Andrulis, Irene L, Miron, Alexander, Hansen, Thomas VO, Caldes, Trinidad, Neuhausen, Susan L, Toland, Amanda E, Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K, Osorio, Ana, Factor, Rachel E, Terry, Mary B, Rebbeck, Timothy R, Karlan, Beth Y, Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul DP, Blows, Fiona M, Dunning, Alison M, Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Slamon, Dennis J, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomäki, Kristiina, Muranen, Taru A, Heikkilä, Päivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J, and Brinton, Louise
Subjects: ABCTB Investigators, EMBRACE Group, GENICA Network, HEBON Group, kConFab Investigators, Humans, Carcinoma, Breast Neoplasms, Receptor, erbB-2, Receptors, Estrogen, Receptors, Progesterone, Neoplasm Staging, Likelihood Functions, Age Factors, Mutation, Genes, BRCA1, Genes, BRCA2, Adult, Aged, Middle Aged, Female, Neoplasm Grading, Triple Negative Breast Neoplasms, Receptor, ErbB-2, Receptor, erbB-2, Receptors, Estrogen, Progesterone, Genes, BRCA1, BRCA2, ErbB-2, Prevention, Breast Cancer, Cancer, Genetics, 4.2 Evaluation of markers and technologies, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract: IntroductionThe distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.MethodsSelection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.ResultsER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).ConclusionsThese results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.
Published: 2014

2. Refined histopathological predictors of BRCA1 and BRCA2mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author: Spurdle, Amanda B, Couch, Fergus J, Parsons, Michael T, McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K, Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L, Domchek, Susan M, Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Åke, Andrulis, Irene L, Miron, Alexander, Hansen, Thomas VO, Caldes, Trinidad, Neuhausen, Susan L, Toland, Amanda E, Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K, Osorio, Ana, Factor, Rachel E, Terry, Mary B, Rebbeck, Timothy R, Karlan, Beth Y, Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul DP, Blows, Fiona M, Dunning, Alison M, Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Slamon, Dennis J, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomäki, Kristiina, Muranen, Taru A, Heikkilä, Päivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J, and Brinton, Louise
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Prevention, Genetics, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Adult, Age Factors, Aged, Breast Neoplasms, Carcinoma, Female, Genes, BRCA1, Genes, BRCA2, Humans, Likelihood Functions, Middle Aged, Mutation, Neoplasm Grading, Neoplasm Staging, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Triple Negative Breast Neoplasms, ABCTB Investigators, EMBRACE Group, GENICA Network, HEBON Group, kConFab Investigators, Receptor, erbB-2, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.
Published: 2014

3. Supplementary Methods, Figures S1 - S3 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P., primary, Beesley, Jonathan, primary, Amin Al Olama, Ali, primary, Michailidou, Kyriaki, primary, Tyrer, Jonathan, primary, Kote-Jarai, ZSofia, primary, Lawrenson, Kate, primary, Lindstrom, Sara, primary, Ramus, Susan J., primary, Thompson, Deborah J., primary, Kibel, Adam S., primary, Dansonka-Mieszkowska, Agnieszka, primary, Michael, Agnieszka, primary, Dieffenbach, Aida K., primary, Gentry-Maharaj, Aleksandra, primary, Whittemore, Alice S., primary, Wolk, Alicja, primary, Monteiro, Alvaro, primary, Peixoto, Ana, primary, Kierzek, Andrzej, primary, Cox, Angela, primary, Rudolph, Anja, primary, Gonzalez-Neira, Anna, primary, Wu, Anna H., primary, Lindblom, Annika, primary, Swerdlow, Anthony, primary, Ziogas, Argyrios, primary, Ekici, Arif B., primary, Burwinkel, Barbara, primary, Karlan, Beth Y., primary, Nordestgaard, Børge G., primary, Blomqvist, Carl, primary, Phelan, Catherine, primary, McLean, Catriona, primary, Pearce, Celeste Leigh, primary, Vachon, Celine, primary, Cybulski, Cezary, primary, Slavov, Chavdar, primary, Stegmaier, Christa, primary, Maier, Christiane, primary, Ambrosone, Christine B., primary, Høgdall, Claus K., primary, Teerlink, Craig C., primary, Kang, Daehee, primary, Tessier, Daniel C., primary, Schaid, Daniel J., primary, Stram, Daniel O., primary, Cramer, Daniel W., primary, Neal, David E., primary, Eccles, Diana, primary, Flesch-Janys, Dieter, primary, Edwards, Digna R. Velez, primary, Wokozorczyk, Dominika, primary, Levine, Douglas A., primary, Yannoukakos, Drakoulis, primary, Sawyer, Elinor J., primary, Bandera, Elisa V., primary, Poole, Elizabeth M., primary, Goode, Ellen L., primary, Khusnutdinova, Elza, primary, Høgdall, Estrid, primary, Song, Fengju, primary, Bruinsma, Fiona, primary, Heitz, Florian, primary, Modugno, Francesmary, primary, Hamdy, Freddie C., primary, Wiklund, Fredrik, primary, Giles, Graham G., primary, Olsson, Håkan, primary, Wildiers, Hans, primary, Ulmer, Hans-Ulrich, primary, Pandha, Hardev, primary, Risch, Harvey A., primary, Darabi, Hatef, primary, Salvesen, Helga B., primary, Nevanlinna, Heli, primary, Gronberg, Henrik, primary, Brenner, Hermann, primary, Brauch, Hiltrud, primary, Anton-Culver, Hoda, primary, Song, Honglin, primary, Lim, Hui-Yi, primary, McNeish, Iain, primary, Campbell, Ian, primary, Vergote, Ignace, primary, Gronwald, Jacek, primary, Lubiński, Jan, primary, Stanford, Janet L., primary, Benítez, Javier, primary, Doherty, Jennifer A., primary, Permuth, Jennifer B., primary, Chang-Claude, Jenny, primary, Donovan, Jenny L., primary, Dennis, Joe, primary, Schildkraut, Joellen M., primary, Schleutker, Johanna, primary, Hopper, John L., primary, Kupryjanczyk, Jolanta, primary, Park, Jong Y., primary, Figueroa, Jonine, primary, Clements, Judith A., primary, Knight, Julia A., primary, Peto, Julian, primary, Cunningham, Julie M., primary, Pow-Sang, Julio, primary, Batra, Jyotsna, primary, Czene, Kamila, primary, Lu, Karen H., primary, Herkommer, Kathleen, primary, Khaw, Kay-Tee, primary, Matsuo, Keitaro, primary, Muir, Kenneth, primary, Offitt, Kenneth, primary, Chen, Kexin, primary, Moysich, Kirsten B., primary, Aittomäki, Kristiina, primary, Odunsi, Kunle, primary, Kiemeney, Lambertus A., primary, Massuger, Leon F.A.G., primary, Fitzgerald, Liesel M., primary, Cook, Linda S., primary, Cannon-Albright, Lisa, primary, Hooning, Maartje J., primary, Pike, Malcolm C., primary, Bolla, Manjeet K., primary, Luedeke, Manuel, primary, Teixeira, Manuel R., primary, Goodman, Marc T., primary, Schmidt, Marjanka K., primary, Riggan, Marjorie, primary, Aly, Markus, primary, Rossing, Mary Anne, primary, Beckmann, Matthias W., primary, Moisse, Matthieu, primary, Sanderson, Maureen, primary, Southey, Melissa C., primary, Jones, Michael, primary, Lush, Michael, primary, Hildebrandt, Michelle A.T., primary, Hou, Ming-Feng, primary, Schoemaker, Minouk J., primary, Garcia-Closas, Montserrat, primary, Bogdanova, Natalia, primary, Rahman, Nazneen, primary, Le, Nhu D., primary, Orr, Nick, primary, Wentzensen, Nicolas, primary, Pashayan, Nora, primary, Peterlongo, Paolo, primary, Guénel, Pascal, primary, Brennan, Paul, primary, Paulo, Paula, primary, Webb, Penelope M., primary, Broberg, Per, primary, Fasching, Peter A., primary, Devilee, Peter, primary, Wang, Qin, primary, Cai, Qiuyin, primary, Li, Qiyuan, primary, Kaneva, Radka, primary, Butzow, Ralf, primary, Kopperud, Reidun Kristin, primary, Schmutzler, Rita K., primary, Stephenson, Robert A., primary, MacInnis, Robert J., primary, Hoover, Robert N., primary, Winqvist, Robert, primary, Ness, Roberta, primary, Milne, Roger L., primary, Travis, Ruth C., primary, Benlloch, Sara, primary, Olson, Sara H., primary, McDonnell, Shannon K., primary, Tworoger, Shelley S., primary, Maia, Sofia, primary, Berndt, Sonja, primary, Lee, Soo Chin, primary, Teo, Soo-Hwang, primary, Thibodeau, Stephen N., primary, Bojesen, Stig E., primary, Gapstur, Susan M., primary, Kjær, Susanne Krüger, primary, Pejovic, Tanja, primary, Tammela, Teuvo L.J., primary, Dörk, Thilo, primary, Brüning, Thomas, primary, Wahlfors, Tiina, primary, Key, Tim J., primary, Edwards, Todd L., primary, Menon, Usha, primary, Hamann, Ute, primary, Mitev, Vanio, primary, Kosma, Veli-Matti, primary, Setiawan, Veronica Wendy, primary, Kristensen, Vessela, primary, Arndt, Volker, primary, Vogel, Walther, primary, Zheng, Wei, primary, Sieh, Weiva, primary, Blot, William J., primary, Kluzniak, Wojciech, primary, Shu, Xiao-Ou, primary, Gao, Yu-Tang, primary, Schumacher, Fredrick, primary, Freedman, Matthew L., primary, Berchuck, Andrew, primary, Dunning, Alison M., primary, Simard, Jacques, primary, Haiman, Christopher A., primary, Spurdle, Amanda, primary, Sellers, Thomas A., primary, Hunter, David J., primary, Henderson, Brian E., primary, Kraft, Peter, primary, Chanock, Stephen J., primary, Couch, Fergus J., primary, Hall, Per, primary, Gayther, Simon A., primary, Easton, Douglas F., primary, Chenevix-Trench, Georgia, primary, Eeles, Rosalind, primary, Pharoah, Paul D.P., primary, and Lambrechts, Diether, primary
Published: 2023
Full Text: View/download PDF

4. Supplementary Tables S1 - S10 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P., primary, Beesley, Jonathan, primary, Amin Al Olama, Ali, primary, Michailidou, Kyriaki, primary, Tyrer, Jonathan, primary, Kote-Jarai, ZSofia, primary, Lawrenson, Kate, primary, Lindstrom, Sara, primary, Ramus, Susan J., primary, Thompson, Deborah J., primary, Kibel, Adam S., primary, Dansonka-Mieszkowska, Agnieszka, primary, Michael, Agnieszka, primary, Dieffenbach, Aida K., primary, Gentry-Maharaj, Aleksandra, primary, Whittemore, Alice S., primary, Wolk, Alicja, primary, Monteiro, Alvaro, primary, Peixoto, Ana, primary, Kierzek, Andrzej, primary, Cox, Angela, primary, Rudolph, Anja, primary, Gonzalez-Neira, Anna, primary, Wu, Anna H., primary, Lindblom, Annika, primary, Swerdlow, Anthony, primary, Ziogas, Argyrios, primary, Ekici, Arif B., primary, Burwinkel, Barbara, primary, Karlan, Beth Y., primary, Nordestgaard, Børge G., primary, Blomqvist, Carl, primary, Phelan, Catherine, primary, McLean, Catriona, primary, Pearce, Celeste Leigh, primary, Vachon, Celine, primary, Cybulski, Cezary, primary, Slavov, Chavdar, primary, Stegmaier, Christa, primary, Maier, Christiane, primary, Ambrosone, Christine B., primary, Høgdall, Claus K., primary, Teerlink, Craig C., primary, Kang, Daehee, primary, Tessier, Daniel C., primary, Schaid, Daniel J., primary, Stram, Daniel O., primary, Cramer, Daniel W., primary, Neal, David E., primary, Eccles, Diana, primary, Flesch-Janys, Dieter, primary, Edwards, Digna R. Velez, primary, Wokozorczyk, Dominika, primary, Levine, Douglas A., primary, Yannoukakos, Drakoulis, primary, Sawyer, Elinor J., primary, Bandera, Elisa V., primary, Poole, Elizabeth M., primary, Goode, Ellen L., primary, Khusnutdinova, Elza, primary, Høgdall, Estrid, primary, Song, Fengju, primary, Bruinsma, Fiona, primary, Heitz, Florian, primary, Modugno, Francesmary, primary, Hamdy, Freddie C., primary, Wiklund, Fredrik, primary, Giles, Graham G., primary, Olsson, Håkan, primary, Wildiers, Hans, primary, Ulmer, Hans-Ulrich, primary, Pandha, Hardev, primary, Risch, Harvey A., primary, Darabi, Hatef, primary, Salvesen, Helga B., primary, Nevanlinna, Heli, primary, Gronberg, Henrik, primary, Brenner, Hermann, primary, Brauch, Hiltrud, primary, Anton-Culver, Hoda, primary, Song, Honglin, primary, Lim, Hui-Yi, primary, McNeish, Iain, primary, Campbell, Ian, primary, Vergote, Ignace, primary, Gronwald, Jacek, primary, Lubiński, Jan, primary, Stanford, Janet L., primary, Benítez, Javier, primary, Doherty, Jennifer A., primary, Permuth, Jennifer B., primary, Chang-Claude, Jenny, primary, Donovan, Jenny L., primary, Dennis, Joe, primary, Schildkraut, Joellen M., primary, Schleutker, Johanna, primary, Hopper, John L., primary, Kupryjanczyk, Jolanta, primary, Park, Jong Y., primary, Figueroa, Jonine, primary, Clements, Judith A., primary, Knight, Julia A., primary, Peto, Julian, primary, Cunningham, Julie M., primary, Pow-Sang, Julio, primary, Batra, Jyotsna, primary, Czene, Kamila, primary, Lu, Karen H., primary, Herkommer, Kathleen, primary, Khaw, Kay-Tee, primary, Matsuo, Keitaro, primary, Muir, Kenneth, primary, Offitt, Kenneth, primary, Chen, Kexin, primary, Moysich, Kirsten B., primary, Aittomäki, Kristiina, primary, Odunsi, Kunle, primary, Kiemeney, Lambertus A., primary, Massuger, Leon F.A.G., primary, Fitzgerald, Liesel M., primary, Cook, Linda S., primary, Cannon-Albright, Lisa, primary, Hooning, Maartje J., primary, Pike, Malcolm C., primary, Bolla, Manjeet K., primary, Luedeke, Manuel, primary, Teixeira, Manuel R., primary, Goodman, Marc T., primary, Schmidt, Marjanka K., primary, Riggan, Marjorie, primary, Aly, Markus, primary, Rossing, Mary Anne, primary, Beckmann, Matthias W., primary, Moisse, Matthieu, primary, Sanderson, Maureen, primary, Southey, Melissa C., primary, Jones, Michael, primary, Lush, Michael, primary, Hildebrandt, Michelle A.T., primary, Hou, Ming-Feng, primary, Schoemaker, Minouk J., primary, Garcia-Closas, Montserrat, primary, Bogdanova, Natalia, primary, Rahman, Nazneen, primary, Le, Nhu D., primary, Orr, Nick, primary, Wentzensen, Nicolas, primary, Pashayan, Nora, primary, Peterlongo, Paolo, primary, Guénel, Pascal, primary, Brennan, Paul, primary, Paulo, Paula, primary, Webb, Penelope M., primary, Broberg, Per, primary, Fasching, Peter A., primary, Devilee, Peter, primary, Wang, Qin, primary, Cai, Qiuyin, primary, Li, Qiyuan, primary, Kaneva, Radka, primary, Butzow, Ralf, primary, Kopperud, Reidun Kristin, primary, Schmutzler, Rita K., primary, Stephenson, Robert A., primary, MacInnis, Robert J., primary, Hoover, Robert N., primary, Winqvist, Robert, primary, Ness, Roberta, primary, Milne, Roger L., primary, Travis, Ruth C., primary, Benlloch, Sara, primary, Olson, Sara H., primary, McDonnell, Shannon K., primary, Tworoger, Shelley S., primary, Maia, Sofia, primary, Berndt, Sonja, primary, Lee, Soo Chin, primary, Teo, Soo-Hwang, primary, Thibodeau, Stephen N., primary, Bojesen, Stig E., primary, Gapstur, Susan M., primary, Kjær, Susanne Krüger, primary, Pejovic, Tanja, primary, Tammela, Teuvo L.J., primary, Dörk, Thilo, primary, Brüning, Thomas, primary, Wahlfors, Tiina, primary, Key, Tim J., primary, Edwards, Todd L., primary, Menon, Usha, primary, Hamann, Ute, primary, Mitev, Vanio, primary, Kosma, Veli-Matti, primary, Setiawan, Veronica Wendy, primary, Kristensen, Vessela, primary, Arndt, Volker, primary, Vogel, Walther, primary, Zheng, Wei, primary, Sieh, Weiva, primary, Blot, William J., primary, Kluzniak, Wojciech, primary, Shu, Xiao-Ou, primary, Gao, Yu-Tang, primary, Schumacher, Fredrick, primary, Freedman, Matthew L., primary, Berchuck, Andrew, primary, Dunning, Alison M., primary, Simard, Jacques, primary, Haiman, Christopher A., primary, Spurdle, Amanda, primary, Sellers, Thomas A., primary, Hunter, David J., primary, Henderson, Brian E., primary, Kraft, Peter, primary, Chanock, Stephen J., primary, Couch, Fergus J., primary, Hall, Per, primary, Gayther, Simon A., primary, Easton, Douglas F., primary, Chenevix-Trench, Georgia, primary, Eeles, Rosalind, primary, Pharoah, Paul D.P., primary, and Lambrechts, Diether, primary
Published: 2023
Full Text: View/download PDF

5. Supplementary Acknowledgments from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P., primary, Beesley, Jonathan, primary, Amin Al Olama, Ali, primary, Michailidou, Kyriaki, primary, Tyrer, Jonathan, primary, Kote-Jarai, ZSofia, primary, Lawrenson, Kate, primary, Lindstrom, Sara, primary, Ramus, Susan J., primary, Thompson, Deborah J., primary, Kibel, Adam S., primary, Dansonka-Mieszkowska, Agnieszka, primary, Michael, Agnieszka, primary, Dieffenbach, Aida K., primary, Gentry-Maharaj, Aleksandra, primary, Whittemore, Alice S., primary, Wolk, Alicja, primary, Monteiro, Alvaro, primary, Peixoto, Ana, primary, Kierzek, Andrzej, primary, Cox, Angela, primary, Rudolph, Anja, primary, Gonzalez-Neira, Anna, primary, Wu, Anna H., primary, Lindblom, Annika, primary, Swerdlow, Anthony, primary, Ziogas, Argyrios, primary, Ekici, Arif B., primary, Burwinkel, Barbara, primary, Karlan, Beth Y., primary, Nordestgaard, Børge G., primary, Blomqvist, Carl, primary, Phelan, Catherine, primary, McLean, Catriona, primary, Pearce, Celeste Leigh, primary, Vachon, Celine, primary, Cybulski, Cezary, primary, Slavov, Chavdar, primary, Stegmaier, Christa, primary, Maier, Christiane, primary, Ambrosone, Christine B., primary, Høgdall, Claus K., primary, Teerlink, Craig C., primary, Kang, Daehee, primary, Tessier, Daniel C., primary, Schaid, Daniel J., primary, Stram, Daniel O., primary, Cramer, Daniel W., primary, Neal, David E., primary, Eccles, Diana, primary, Flesch-Janys, Dieter, primary, Edwards, Digna R. Velez, primary, Wokozorczyk, Dominika, primary, Levine, Douglas A., primary, Yannoukakos, Drakoulis, primary, Sawyer, Elinor J., primary, Bandera, Elisa V., primary, Poole, Elizabeth M., primary, Goode, Ellen L., primary, Khusnutdinova, Elza, primary, Høgdall, Estrid, primary, Song, Fengju, primary, Bruinsma, Fiona, primary, Heitz, Florian, primary, Modugno, Francesmary, primary, Hamdy, Freddie C., primary, Wiklund, Fredrik, primary, Giles, Graham G., primary, Olsson, Håkan, primary, Wildiers, Hans, primary, Ulmer, Hans-Ulrich, primary, Pandha, Hardev, primary, Risch, Harvey A., primary, Darabi, Hatef, primary, Salvesen, Helga B., primary, Nevanlinna, Heli, primary, Gronberg, Henrik, primary, Brenner, Hermann, primary, Brauch, Hiltrud, primary, Anton-Culver, Hoda, primary, Song, Honglin, primary, Lim, Hui-Yi, primary, McNeish, Iain, primary, Campbell, Ian, primary, Vergote, Ignace, primary, Gronwald, Jacek, primary, Lubiński, Jan, primary, Stanford, Janet L., primary, Benítez, Javier, primary, Doherty, Jennifer A., primary, Permuth, Jennifer B., primary, Chang-Claude, Jenny, primary, Donovan, Jenny L., primary, Dennis, Joe, primary, Schildkraut, Joellen M., primary, Schleutker, Johanna, primary, Hopper, John L., primary, Kupryjanczyk, Jolanta, primary, Park, Jong Y., primary, Figueroa, Jonine, primary, Clements, Judith A., primary, Knight, Julia A., primary, Peto, Julian, primary, Cunningham, Julie M., primary, Pow-Sang, Julio, primary, Batra, Jyotsna, primary, Czene, Kamila, primary, Lu, Karen H., primary, Herkommer, Kathleen, primary, Khaw, Kay-Tee, primary, Matsuo, Keitaro, primary, Muir, Kenneth, primary, Offitt, Kenneth, primary, Chen, Kexin, primary, Moysich, Kirsten B., primary, Aittomäki, Kristiina, primary, Odunsi, Kunle, primary, Kiemeney, Lambertus A., primary, Massuger, Leon F.A.G., primary, Fitzgerald, Liesel M., primary, Cook, Linda S., primary, Cannon-Albright, Lisa, primary, Hooning, Maartje J., primary, Pike, Malcolm C., primary, Bolla, Manjeet K., primary, Luedeke, Manuel, primary, Teixeira, Manuel R., primary, Goodman, Marc T., primary, Schmidt, Marjanka K., primary, Riggan, Marjorie, primary, Aly, Markus, primary, Rossing, Mary Anne, primary, Beckmann, Matthias W., primary, Moisse, Matthieu, primary, Sanderson, Maureen, primary, Southey, Melissa C., primary, Jones, Michael, primary, Lush, Michael, primary, Hildebrandt, Michelle A.T., primary, Hou, Ming-Feng, primary, Schoemaker, Minouk J., primary, Garcia-Closas, Montserrat, primary, Bogdanova, Natalia, primary, Rahman, Nazneen, primary, Le, Nhu D., primary, Orr, Nick, primary, Wentzensen, Nicolas, primary, Pashayan, Nora, primary, Peterlongo, Paolo, primary, Guénel, Pascal, primary, Brennan, Paul, primary, Paulo, Paula, primary, Webb, Penelope M., primary, Broberg, Per, primary, Fasching, Peter A., primary, Devilee, Peter, primary, Wang, Qin, primary, Cai, Qiuyin, primary, Li, Qiyuan, primary, Kaneva, Radka, primary, Butzow, Ralf, primary, Kopperud, Reidun Kristin, primary, Schmutzler, Rita K., primary, Stephenson, Robert A., primary, MacInnis, Robert J., primary, Hoover, Robert N., primary, Winqvist, Robert, primary, Ness, Roberta, primary, Milne, Roger L., primary, Travis, Ruth C., primary, Benlloch, Sara, primary, Olson, Sara H., primary, McDonnell, Shannon K., primary, Tworoger, Shelley S., primary, Maia, Sofia, primary, Berndt, Sonja, primary, Lee, Soo Chin, primary, Teo, Soo-Hwang, primary, Thibodeau, Stephen N., primary, Bojesen, Stig E., primary, Gapstur, Susan M., primary, Kjær, Susanne Krüger, primary, Pejovic, Tanja, primary, Tammela, Teuvo L.J., primary, Dörk, Thilo, primary, Brüning, Thomas, primary, Wahlfors, Tiina, primary, Key, Tim J., primary, Edwards, Todd L., primary, Menon, Usha, primary, Hamann, Ute, primary, Mitev, Vanio, primary, Kosma, Veli-Matti, primary, Setiawan, Veronica Wendy, primary, Kristensen, Vessela, primary, Arndt, Volker, primary, Vogel, Walther, primary, Zheng, Wei, primary, Sieh, Weiva, primary, Blot, William J., primary, Kluzniak, Wojciech, primary, Shu, Xiao-Ou, primary, Gao, Yu-Tang, primary, Schumacher, Fredrick, primary, Freedman, Matthew L., primary, Berchuck, Andrew, primary, Dunning, Alison M., primary, Simard, Jacques, primary, Haiman, Christopher A., primary, Spurdle, Amanda, primary, Sellers, Thomas A., primary, Hunter, David J., primary, Henderson, Brian E., primary, Kraft, Peter, primary, Chanock, Stephen J., primary, Couch, Fergus J., primary, Hall, Per, primary, Gayther, Simon A., primary, Easton, Douglas F., primary, Chenevix-Trench, Georgia, primary, Eeles, Rosalind, primary, Pharoah, Paul D.P., primary, and Lambrechts, Diether, primary
Published: 2023
Full Text: View/download PDF

6. Data from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P., primary, Beesley, Jonathan, primary, Amin Al Olama, Ali, primary, Michailidou, Kyriaki, primary, Tyrer, Jonathan, primary, Kote-Jarai, ZSofia, primary, Lawrenson, Kate, primary, Lindstrom, Sara, primary, Ramus, Susan J., primary, Thompson, Deborah J., primary, Kibel, Adam S., primary, Dansonka-Mieszkowska, Agnieszka, primary, Michael, Agnieszka, primary, Dieffenbach, Aida K., primary, Gentry-Maharaj, Aleksandra, primary, Whittemore, Alice S., primary, Wolk, Alicja, primary, Monteiro, Alvaro, primary, Peixoto, Ana, primary, Kierzek, Andrzej, primary, Cox, Angela, primary, Rudolph, Anja, primary, Gonzalez-Neira, Anna, primary, Wu, Anna H., primary, Lindblom, Annika, primary, Swerdlow, Anthony, primary, Ziogas, Argyrios, primary, Ekici, Arif B., primary, Burwinkel, Barbara, primary, Karlan, Beth Y., primary, Nordestgaard, Børge G., primary, Blomqvist, Carl, primary, Phelan, Catherine, primary, McLean, Catriona, primary, Pearce, Celeste Leigh, primary, Vachon, Celine, primary, Cybulski, Cezary, primary, Slavov, Chavdar, primary, Stegmaier, Christa, primary, Maier, Christiane, primary, Ambrosone, Christine B., primary, Høgdall, Claus K., primary, Teerlink, Craig C., primary, Kang, Daehee, primary, Tessier, Daniel C., primary, Schaid, Daniel J., primary, Stram, Daniel O., primary, Cramer, Daniel W., primary, Neal, David E., primary, Eccles, Diana, primary, Flesch-Janys, Dieter, primary, Edwards, Digna R. Velez, primary, Wokozorczyk, Dominika, primary, Levine, Douglas A., primary, Yannoukakos, Drakoulis, primary, Sawyer, Elinor J., primary, Bandera, Elisa V., primary, Poole, Elizabeth M., primary, Goode, Ellen L., primary, Khusnutdinova, Elza, primary, Høgdall, Estrid, primary, Song, Fengju, primary, Bruinsma, Fiona, primary, Heitz, Florian, primary, Modugno, Francesmary, primary, Hamdy, Freddie C., primary, Wiklund, Fredrik, primary, Giles, Graham G., primary, Olsson, Håkan, primary, Wildiers, Hans, primary, Ulmer, Hans-Ulrich, primary, Pandha, Hardev, primary, Risch, Harvey A., primary, Darabi, Hatef, primary, Salvesen, Helga B., primary, Nevanlinna, Heli, primary, Gronberg, Henrik, primary, Brenner, Hermann, primary, Brauch, Hiltrud, primary, Anton-Culver, Hoda, primary, Song, Honglin, primary, Lim, Hui-Yi, primary, McNeish, Iain, primary, Campbell, Ian, primary, Vergote, Ignace, primary, Gronwald, Jacek, primary, Lubiński, Jan, primary, Stanford, Janet L., primary, Benítez, Javier, primary, Doherty, Jennifer A., primary, Permuth, Jennifer B., primary, Chang-Claude, Jenny, primary, Donovan, Jenny L., primary, Dennis, Joe, primary, Schildkraut, Joellen M., primary, Schleutker, Johanna, primary, Hopper, John L., primary, Kupryjanczyk, Jolanta, primary, Park, Jong Y., primary, Figueroa, Jonine, primary, Clements, Judith A., primary, Knight, Julia A., primary, Peto, Julian, primary, Cunningham, Julie M., primary, Pow-Sang, Julio, primary, Batra, Jyotsna, primary, Czene, Kamila, primary, Lu, Karen H., primary, Herkommer, Kathleen, primary, Khaw, Kay-Tee, primary, Matsuo, Keitaro, primary, Muir, Kenneth, primary, Offitt, Kenneth, primary, Chen, Kexin, primary, Moysich, Kirsten B., primary, Aittomäki, Kristiina, primary, Odunsi, Kunle, primary, Kiemeney, Lambertus A., primary, Massuger, Leon F.A.G., primary, Fitzgerald, Liesel M., primary, Cook, Linda S., primary, Cannon-Albright, Lisa, primary, Hooning, Maartje J., primary, Pike, Malcolm C., primary, Bolla, Manjeet K., primary, Luedeke, Manuel, primary, Teixeira, Manuel R., primary, Goodman, Marc T., primary, Schmidt, Marjanka K., primary, Riggan, Marjorie, primary, Aly, Markus, primary, Rossing, Mary Anne, primary, Beckmann, Matthias W., primary, Moisse, Matthieu, primary, Sanderson, Maureen, primary, Southey, Melissa C., primary, Jones, Michael, primary, Lush, Michael, primary, Hildebrandt, Michelle A.T., primary, Hou, Ming-Feng, primary, Schoemaker, Minouk J., primary, Garcia-Closas, Montserrat, primary, Bogdanova, Natalia, primary, Rahman, Nazneen, primary, Le, Nhu D., primary, Orr, Nick, primary, Wentzensen, Nicolas, primary, Pashayan, Nora, primary, Peterlongo, Paolo, primary, Guénel, Pascal, primary, Brennan, Paul, primary, Paulo, Paula, primary, Webb, Penelope M., primary, Broberg, Per, primary, Fasching, Peter A., primary, Devilee, Peter, primary, Wang, Qin, primary, Cai, Qiuyin, primary, Li, Qiyuan, primary, Kaneva, Radka, primary, Butzow, Ralf, primary, Kopperud, Reidun Kristin, primary, Schmutzler, Rita K., primary, Stephenson, Robert A., primary, MacInnis, Robert J., primary, Hoover, Robert N., primary, Winqvist, Robert, primary, Ness, Roberta, primary, Milne, Roger L., primary, Travis, Ruth C., primary, Benlloch, Sara, primary, Olson, Sara H., primary, McDonnell, Shannon K., primary, Tworoger, Shelley S., primary, Maia, Sofia, primary, Berndt, Sonja, primary, Lee, Soo Chin, primary, Teo, Soo-Hwang, primary, Thibodeau, Stephen N., primary, Bojesen, Stig E., primary, Gapstur, Susan M., primary, Kjær, Susanne Krüger, primary, Pejovic, Tanja, primary, Tammela, Teuvo L.J., primary, Dörk, Thilo, primary, Brüning, Thomas, primary, Wahlfors, Tiina, primary, Key, Tim J., primary, Edwards, Todd L., primary, Menon, Usha, primary, Hamann, Ute, primary, Mitev, Vanio, primary, Kosma, Veli-Matti, primary, Setiawan, Veronica Wendy, primary, Kristensen, Vessela, primary, Arndt, Volker, primary, Vogel, Walther, primary, Zheng, Wei, primary, Sieh, Weiva, primary, Blot, William J., primary, Kluzniak, Wojciech, primary, Shu, Xiao-Ou, primary, Gao, Yu-Tang, primary, Schumacher, Fredrick, primary, Freedman, Matthew L., primary, Berchuck, Andrew, primary, Dunning, Alison M., primary, Simard, Jacques, primary, Haiman, Christopher A., primary, Spurdle, Amanda, primary, Sellers, Thomas A., primary, Hunter, David J., primary, Henderson, Brian E., primary, Kraft, Peter, primary, Chanock, Stephen J., primary, Couch, Fergus J., primary, Hall, Per, primary, Gayther, Simon A., primary, Easton, Douglas F., primary, Chenevix-Trench, Georgia, primary, Eeles, Rosalind, primary, Pharoah, Paul D.P., primary, and Lambrechts, Diether, primary
Published: 2023
Full Text: View/download PDF

7. Supplementary Grant Support from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P., primary, Beesley, Jonathan, primary, Amin Al Olama, Ali, primary, Michailidou, Kyriaki, primary, Tyrer, Jonathan, primary, Kote-Jarai, ZSofia, primary, Lawrenson, Kate, primary, Lindstrom, Sara, primary, Ramus, Susan J., primary, Thompson, Deborah J., primary, Kibel, Adam S., primary, Dansonka-Mieszkowska, Agnieszka, primary, Michael, Agnieszka, primary, Dieffenbach, Aida K., primary, Gentry-Maharaj, Aleksandra, primary, Whittemore, Alice S., primary, Wolk, Alicja, primary, Monteiro, Alvaro, primary, Peixoto, Ana, primary, Kierzek, Andrzej, primary, Cox, Angela, primary, Rudolph, Anja, primary, Gonzalez-Neira, Anna, primary, Wu, Anna H., primary, Lindblom, Annika, primary, Swerdlow, Anthony, primary, Ziogas, Argyrios, primary, Ekici, Arif B., primary, Burwinkel, Barbara, primary, Karlan, Beth Y., primary, Nordestgaard, Børge G., primary, Blomqvist, Carl, primary, Phelan, Catherine, primary, McLean, Catriona, primary, Pearce, Celeste Leigh, primary, Vachon, Celine, primary, Cybulski, Cezary, primary, Slavov, Chavdar, primary, Stegmaier, Christa, primary, Maier, Christiane, primary, Ambrosone, Christine B., primary, Høgdall, Claus K., primary, Teerlink, Craig C., primary, Kang, Daehee, primary, Tessier, Daniel C., primary, Schaid, Daniel J., primary, Stram, Daniel O., primary, Cramer, Daniel W., primary, Neal, David E., primary, Eccles, Diana, primary, Flesch-Janys, Dieter, primary, Edwards, Digna R. Velez, primary, Wokozorczyk, Dominika, primary, Levine, Douglas A., primary, Yannoukakos, Drakoulis, primary, Sawyer, Elinor J., primary, Bandera, Elisa V., primary, Poole, Elizabeth M., primary, Goode, Ellen L., primary, Khusnutdinova, Elza, primary, Høgdall, Estrid, primary, Song, Fengju, primary, Bruinsma, Fiona, primary, Heitz, Florian, primary, Modugno, Francesmary, primary, Hamdy, Freddie C., primary, Wiklund, Fredrik, primary, Giles, Graham G., primary, Olsson, Håkan, primary, Wildiers, Hans, primary, Ulmer, Hans-Ulrich, primary, Pandha, Hardev, primary, Risch, Harvey A., primary, Darabi, Hatef, primary, Salvesen, Helga B., primary, Nevanlinna, Heli, primary, Gronberg, Henrik, primary, Brenner, Hermann, primary, Brauch, Hiltrud, primary, Anton-Culver, Hoda, primary, Song, Honglin, primary, Lim, Hui-Yi, primary, McNeish, Iain, primary, Campbell, Ian, primary, Vergote, Ignace, primary, Gronwald, Jacek, primary, Lubiński, Jan, primary, Stanford, Janet L., primary, Benítez, Javier, primary, Doherty, Jennifer A., primary, Permuth, Jennifer B., primary, Chang-Claude, Jenny, primary, Donovan, Jenny L., primary, Dennis, Joe, primary, Schildkraut, Joellen M., primary, Schleutker, Johanna, primary, Hopper, John L., primary, Kupryjanczyk, Jolanta, primary, Park, Jong Y., primary, Figueroa, Jonine, primary, Clements, Judith A., primary, Knight, Julia A., primary, Peto, Julian, primary, Cunningham, Julie M., primary, Pow-Sang, Julio, primary, Batra, Jyotsna, primary, Czene, Kamila, primary, Lu, Karen H., primary, Herkommer, Kathleen, primary, Khaw, Kay-Tee, primary, Matsuo, Keitaro, primary, Muir, Kenneth, primary, Offitt, Kenneth, primary, Chen, Kexin, primary, Moysich, Kirsten B., primary, Aittomäki, Kristiina, primary, Odunsi, Kunle, primary, Kiemeney, Lambertus A., primary, Massuger, Leon F.A.G., primary, Fitzgerald, Liesel M., primary, Cook, Linda S., primary, Cannon-Albright, Lisa, primary, Hooning, Maartje J., primary, Pike, Malcolm C., primary, Bolla, Manjeet K., primary, Luedeke, Manuel, primary, Teixeira, Manuel R., primary, Goodman, Marc T., primary, Schmidt, Marjanka K., primary, Riggan, Marjorie, primary, Aly, Markus, primary, Rossing, Mary Anne, primary, Beckmann, Matthias W., primary, Moisse, Matthieu, primary, Sanderson, Maureen, primary, Southey, Melissa C., primary, Jones, Michael, primary, Lush, Michael, primary, Hildebrandt, Michelle A.T., primary, Hou, Ming-Feng, primary, Schoemaker, Minouk J., primary, Garcia-Closas, Montserrat, primary, Bogdanova, Natalia, primary, Rahman, Nazneen, primary, Le, Nhu D., primary, Orr, Nick, primary, Wentzensen, Nicolas, primary, Pashayan, Nora, primary, Peterlongo, Paolo, primary, Guénel, Pascal, primary, Brennan, Paul, primary, Paulo, Paula, primary, Webb, Penelope M., primary, Broberg, Per, primary, Fasching, Peter A., primary, Devilee, Peter, primary, Wang, Qin, primary, Cai, Qiuyin, primary, Li, Qiyuan, primary, Kaneva, Radka, primary, Butzow, Ralf, primary, Kopperud, Reidun Kristin, primary, Schmutzler, Rita K., primary, Stephenson, Robert A., primary, MacInnis, Robert J., primary, Hoover, Robert N., primary, Winqvist, Robert, primary, Ness, Roberta, primary, Milne, Roger L., primary, Travis, Ruth C., primary, Benlloch, Sara, primary, Olson, Sara H., primary, McDonnell, Shannon K., primary, Tworoger, Shelley S., primary, Maia, Sofia, primary, Berndt, Sonja, primary, Lee, Soo Chin, primary, Teo, Soo-Hwang, primary, Thibodeau, Stephen N., primary, Bojesen, Stig E., primary, Gapstur, Susan M., primary, Kjær, Susanne Krüger, primary, Pejovic, Tanja, primary, Tammela, Teuvo L.J., primary, Dörk, Thilo, primary, Brüning, Thomas, primary, Wahlfors, Tiina, primary, Key, Tim J., primary, Edwards, Todd L., primary, Menon, Usha, primary, Hamann, Ute, primary, Mitev, Vanio, primary, Kosma, Veli-Matti, primary, Setiawan, Veronica Wendy, primary, Kristensen, Vessela, primary, Arndt, Volker, primary, Vogel, Walther, primary, Zheng, Wei, primary, Sieh, Weiva, primary, Blot, William J., primary, Kluzniak, Wojciech, primary, Shu, Xiao-Ou, primary, Gao, Yu-Tang, primary, Schumacher, Fredrick, primary, Freedman, Matthew L., primary, Berchuck, Andrew, primary, Dunning, Alison M., primary, Simard, Jacques, primary, Haiman, Christopher A., primary, Spurdle, Amanda, primary, Sellers, Thomas A., primary, Hunter, David J., primary, Henderson, Brian E., primary, Kraft, Peter, primary, Chanock, Stephen J., primary, Couch, Fergus J., primary, Hall, Per, primary, Gayther, Simon A., primary, Easton, Douglas F., primary, Chenevix-Trench, Georgia, primary, Eeles, Rosalind, primary, Pharoah, Paul D.P., primary, and Lambrechts, Diether, primary
Published: 2023
Full Text: View/download PDF

8. Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies

Author: Vos, Elvira L., primary, Salo-Mullen, Erin E., additional, Tang, Laura H., additional, Schattner, Mark, additional, Yoon, Sam S., additional, Gerdes, Hans, additional, Markowitz, Arnold J., additional, Mandelker, Diana, additional, Janjigian, Yelena, additional, Offitt, Kenneth, additional, Coit, Daniel G., additional, Stadler, Zsofia K., additional, and Strong, Vivian E., additional
Published: 2020
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9. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

Author: Wang, Xiaoliang, Dai, James Y, Albanes, Demetrius, Arndt, Volker, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Buchanan, Daniel D, Butterbach, Katja, Caan, Bette, Casey, Graham, Campbell, Peter T, Chan, Andrew T, Chen, Zhengyi, Chang-Claude, Jenny, Cotterchio, Michelle, Easton, Douglas F, Giles, Graham G, Giovannucci, Edward, Grady, William M, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Jenkins, Mark A, Joshi, Amit D, Lampe, Johanna W, Larsson, Susanna C, Lejbkowicz, Flavio, Li, Li, Lindblom, Annika, Le Marchand, Loic, Martin, Vicente, Milne, Roger L, Moreno, Victor, Newcomb, Polly A, Offitt, Kenneth, Ogino, Shuji, Pharoah, Paul D P, Pinchev, Mila, Potter, John D, Rennert, Hedy S, Rennert, Gad, Saliba, Walid, Schafmayer, Clemens, Schoen, Robert E, Schrotz-King, Petra, Slattery, Martha L, Song, Mingyang, Stegmaier, Christa, Weinstein, Stephanie J, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Gruber, Stephen B, Peters, Ulrike, White, Emily, Wang, Xiaoliang, Dai, James Y, Albanes, Demetrius, Arndt, Volker, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Buchanan, Daniel D, Butterbach, Katja, Caan, Bette, Casey, Graham, Campbell, Peter T, Chan, Andrew T, Chen, Zhengyi, Chang-Claude, Jenny, Cotterchio, Michelle, Easton, Douglas F, Giles, Graham G, Giovannucci, Edward, Grady, William M, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Jenkins, Mark A, Joshi, Amit D, Lampe, Johanna W, Larsson, Susanna C, Lejbkowicz, Flavio, Li, Li, Lindblom, Annika, Le Marchand, Loic, Martin, Vicente, Milne, Roger L, Moreno, Victor, Newcomb, Polly A, Offitt, Kenneth, Ogino, Shuji, Pharoah, Paul D P, Pinchev, Mila, Potter, John D, Rennert, Hedy S, Rennert, Gad, Saliba, Walid, Schafmayer, Clemens, Schoen, Robert E, Schrotz-King, Petra, Slattery, Martha L, Song, Mingyang, Stegmaier, Christa, Weinstein, Stephanie J, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Gruber, Stephen B, Peters, Ulrike, and White, Emily
Abstract: Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.
Published: 2019
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10. The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity

Author: Colombo, Mara, Lopez-Perolio, Irene, Meeks, Huong D., Caleca, Laura, Parsons, Michael T., Li, Hongyan, De Vecchi, Giovanna, Tudini, Emma, Foglia, Claudia, Mondini, Patrizia, Manoukian, Siranoush, Behar, Raquel, Garcia, Encarna B. Gomez, Meindl, Alfons, Montagna, Marco, Niederacher, Dieter, Schmidt, Ane Y., Varesco, Liliana, Wappenschmidt, Barbara, Bolla, Manjeet K., Dennis, Joe, Michailidou, Kyriaki, Wang, Qin, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Beckmann, Matthias W., Beeghly-Fadel, Alicia, Benitez, Javier, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Chang-Claude, Jenny, Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Devilee, Peter, Dork, Thilo, Eriksson, Mikael, Fasching, Peter A., Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Gabrielson, Marike, Garcia-Closas, Montserrat, Giles, Graham G., Gonzalez-Neira, Anna, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hartman, Mikael, Hauke, Jan, Hollestelle, Antoinette, Hopper, John L., Jakubowska, Anna, Jung, Audrey, Kosma, Veli-Matti, Lambrechts, Diether, Le Marchand, Loid, Lindblom, Annika, Lubinski, Jan, Mannermaa, Arto, Margolin, Sara, Miao, Hui, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Olson, Janet E., Peterlongo, Paolo, Peto, Julian, Pylkas, Katri, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., See, Mee Hoong, Southey, Melissa C., Swerdlow, Anthony, Teo, Soo H., Toland, Amanda E., Tomlinson, Ian, Truong, Therese, van Asperen, Christi J., van den Ouweland, Ans M. W., van der Kolk, Lizet E., Winqvist, Robert, Yannoukakos, Drakoulis, Zheng, Wei, Dunning, Alison M., Easton, Douglas F., Henderson, Alex, Hogervorst, Frans B. L., Izatt, Louise, Offitt, Kenneth, Side, Lucy E., van Rensburg, Elizabeth J., McGuffog, Lesley, Antoniou, Antonis C., Chenevix-Trench, Georgia, Spurdle, Amanda B., Goldgar, David E., de la Hoya, Miguel, Radice, Paolo, Colombo, Mara, Lopez-Perolio, Irene, Meeks, Huong D., Caleca, Laura, Parsons, Michael T., Li, Hongyan, De Vecchi, Giovanna, Tudini, Emma, Foglia, Claudia, Mondini, Patrizia, Manoukian, Siranoush, Behar, Raquel, Garcia, Encarna B. Gomez, Meindl, Alfons, Montagna, Marco, Niederacher, Dieter, Schmidt, Ane Y., Varesco, Liliana, Wappenschmidt, Barbara, Bolla, Manjeet K., Dennis, Joe, Michailidou, Kyriaki, Wang, Qin, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Beckmann, Matthias W., Beeghly-Fadel, Alicia, Benitez, Javier, Boeckx, Bram, Bogdanova, Natalia V., Bojesen, Stig E., Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Chang-Claude, Jenny, Conroy, Don M., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Devilee, Peter, Dork, Thilo, Eriksson, Mikael, Fasching, Peter A., Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Gabrielson, Marike, Garcia-Closas, Montserrat, Giles, Graham G., Gonzalez-Neira, Anna, Guenel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hartman, Mikael, Hauke, Jan, Hollestelle, Antoinette, Hopper, John L., Jakubowska, Anna, Jung, Audrey, Kosma, Veli-Matti, Lambrechts, Diether, Le Marchand, Loid, Lindblom, Annika, Lubinski, Jan, Mannermaa, Arto, Margolin, Sara, Miao, Hui, Milne, Roger L., Neuhausen, Susan L., Nevanlinna, Heli, Olson, Janet E., Peterlongo, Paolo, Peto, Julian, Pylkas, Katri, Sawyer, Elinor J., Schmidt, Marjanka K., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., See, Mee Hoong, Southey, Melissa C., Swerdlow, Anthony, Teo, Soo H., Toland, Amanda E., Tomlinson, Ian, Truong, Therese, van Asperen, Christi J., van den Ouweland, Ans M. W., van der Kolk, Lizet E., Winqvist, Robert, Yannoukakos, Drakoulis, Zheng, Wei, Dunning, Alison M., Easton, Douglas F., Henderson, Alex, Hogervorst, Frans B. L., Izatt, Louise, Offitt, Kenneth, Side, Lucy E., van Rensburg, Elizabeth J., McGuffog, Lesley, Antoniou, Antonis C., Chenevix-Trench, Georgia, Spurdle, Amanda B., Goldgar, David E., de la Hoya, Miguel, and Radice, Paolo
Abstract: Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44x10(-115). There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.
Published: 2018

11. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

Author: Wang, Xiaoliang, primary, Dai, James Y, additional, Albanes, Demetrius, additional, Arndt, Volker, additional, Berndt, Sonja I, additional, Bézieau, Stéphane, additional, Brenner, Hermann, additional, Buchanan, Daniel D, additional, Butterbach, Katja, additional, Caan, Bette, additional, Casey, Graham, additional, Campbell, Peter T, additional, Chan, Andrew T, additional, Chen, Zhengyi, additional, Chang-Claude, Jenny, additional, Cotterchio, Michelle, additional, Easton, Douglas F, additional, Giles, Graham G, additional, Giovannucci, Edward, additional, Grady, William M, additional, Hoffmeister, Michael, additional, Hopper, John L, additional, Hsu, Li, additional, Jenkins, Mark A, additional, Joshi, Amit D, additional, Lampe, Johanna W, additional, Larsson, Susanna C, additional, Lejbkowicz, Flavio, additional, Li, Li, additional, Lindblom, Annika, additional, Le Marchand, Loic, additional, Martin, Vicente, additional, Milne, Roger L, additional, Moreno, Victor, additional, Newcomb, Polly A, additional, Offitt, Kenneth, additional, Ogino, Shuji, additional, Pharoah, Paul D P, additional, Pinchev, Mila, additional, Potter, John D, additional, Rennert, Hedy S, additional, Rennert, Gad, additional, Saliba, Walid, additional, Schafmayer, Clemens, additional, Schoen, Robert E, additional, Schrotz-King, Petra, additional, Slattery, Martha L, additional, Song, Mingyang, additional, Stegmaier, Christa, additional, Weinstein, Stephanie J, additional, Wolk, Alicja, additional, Woods, Michael O, additional, Wu, Anna H, additional, Gruber, Stephen B, additional, Peters, Ulrike, additional, and White, Emily, additional
Published: 2018
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12. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P., Beesley, Jonathan, Al Olama, Ali Amin, Michailidou, Kyriaki, Tyrer, Jonathan, Kote-Jarai, Zsofi A., Lawrenson, Kate, Lindstrom, Sara, Ramus, Susan J., Thompson, Deborah J., Kibel, Adam S., Dansonka-Mieszkowska, Agnieszka, Michael, Agnieszka, Dieffenbach, Aida K., Gentry-Maharaj, Aleksandra, Whittemore, Alice S., Wolk, Alicja, Monteiro, Alvaro, Peixoto, Ana, Kierzek, Andrzej, Cox, Angela, Rudolph, Anja, Gonzalez-Neira, Anna, Wu, Anna H., Lindblom, Annika, Swerdlow, Anthony, Ziogas, Argyrios, Ekici, Arif B., Burwinkel, Barbara, Karlan, Beth Y., Nordestgaard, Borge G., Blomqvist, Carl, Phelan, Catherine, McLean, Catriona, Pearce, Celeste Leigh, Vachon, Celine, Cybulski, Cezary, Slavov, Chavdar, Stegmaier, Christa, Maier, Christiane, Ambrosone, Christine B., Hogdall, Claus K., Teerlink, Craig C., Kang, Daehee, Tessier, Daniel C., Schaid, Daniel J., Stram, Daniel O., Cramer, Daniel W., Neal, David E., Eccles, Diana, Flesch-Janys, Dieter, Edwards, Digna R. Velez, Wokozorczyk, Dominika, Levine, Douglas A., Yannoukakos, Drakoulis, Sawyer, Elinor J., Bandera, Elisa V., Poole, Elizabeth M., Goode, Ellen L., Khusnutdinova, Elza, Hogdall, Estrid, Song, Fengju, Bruinsma, Fiona, Heitz, Florian, Modugno, Francesmary, Hamdy, Freddie C., Wiklund, Fredrik, Giles, Graham G., Olsson, Hakan, Wildiers, Hans, Ulmer, Hans-Ulrich, Pandha, Hardev, Risch, Harvey A., Darabi, Hatef, Salvesen, Helga B., Nevanlinna, Heli, Gronberg, Henrik, Brenner, Hermann, Brauch, Hiltrud, Anton-Culver, Hoda, Song, Honglin, Lim, Hui-Yi, McNeish, Iain, Campbell, Ian, Vergote, Ignace, Gronwald, Jacek, Lubinski, Jan, Stanford, Janet L., Bentez, Javier, Doherty, Jennifer A., Permuth, Jennifer B., Chang-Claude, Jenny, Donovan, Jenny L., Dennis, Joe, Schildkraut, Joellen M., Schleutker, Johanna, Hopper, John L., Kupryjanczyk, Jolanta, Park, Jong Y., Figueroa, Jonine, Clements, Judith A., Knight, Julia A., Peto, Julian, Cunningham, Julie M., Pow-Sang, Julio, Batra, Jyotsna, Czene, Kamila, Lu, Karen H., Herkommer, Kathleen, Khaw, Kay-Tee, Matsuo, Keitaro, Muir, Kenneth, Offitt, Kenneth, Chen, Kexin, Moysich, Kirsten B., Aittomaki, Kristiina, Odunsi, Kunle, Kiemeney, Lambertus A., Massuger, Leon F. A. G., Fitzgerald, Liesel M., Cook, Linda S., Cannon-Albright, Lisa, Hooning, Maartje J., Pike, Malcolm C., Bolla, Manjeet K., Luedeke, Manuel, Teixeira, Manuel R., Goodman, Marc T., Schmidt, Marjanka K., Riggan, Marjorie, Aly, Markus, Rossing, Mary Anne, Beckmann, Matthias W., Moisse, Matthieu, Sanderson, Maureen, Southey, Melissa C., Jones, Michael, Lush, Michael, Hildebrandt, Michelle A. T., Hou, Ming-Feng, Schoemaker, Minouk J., Garcia-Closas, Montserrat, Bogdanova, Natalia, Rahman, Nazneen, Le, Nhu D., Orr, Nick, Wentzensen, Nicolas, Pashayan, Nora, Peterlongo, Paolo, Guenel, Pascal, Brennan, Paul, Paulo, Paula, Webb, Penelope M., Broberg, Per, Fasching, Peter A., Devilee, Peter, Wang, Qin, Cai, Qiuyin, Li, Qiyuan, Kaneva, Radka, Butzow, Ralf, Kopperud, Reidun Kristin, Schmutzler, Rita K., Stephenson, Robert A., MacInnis, Robert J., Hoover, Robert N., Winqvist, Robert, Ness, Roberta, Milne, Roger L., Travis, Ruth C., Benlloch, Sara, Olson, Sara H., McDonnell, Shannon K., Tworoger, Shelley S., Maia, Sofi A., Berndt, Sonja, Lee, Soo Chin, Teo, Soo-Hwang, Thibodeau, Stephen N., Bojesen, Stig E., Gapstur, Susan M., Kjaer, Susanne Krueger, Pejovic, Tanja, Tammela, Teuvo L. J., Doerk, Thilo, Bruening, Thomas, Wahlfors, Tiina, Key, Tim J., Edwards, Todd L., Menon, Usha, Hamann, Ute, Mitev, Vanio, Kosma, Veli-Matti, Setiawan, Veronica Wendy, Kristensen, Vessela, Arndt, Volker, Vogel, Walther, Zheng, Wei, Sieh, Weiva, Blot, William J., Kluzniak, Wojciech, Shu, Xiao-Ou, Gao, Yu-Tang, Schumacher, Fredrick, Freedman, Matthew L., Berchuck, Andrew, Dunning, Alison M., Simard, Jacques, Haiman, Christopher A., Spurdle, Amanda, Sellers, Thomas A., Hunter, David J., Henderson, Brian E., Kraft, Peter, Chanock, Stephen J., Couch, Fergus J., Hall, Per, Gayther, Simon A., Easton, Douglas F., Chenevix-Trench, Georgia, Eeles, Rosalind, Pharoah, Paul D. P., Lambrechts, Diether, Kar, Siddhartha P., Beesley, Jonathan, Al Olama, Ali Amin, Michailidou, Kyriaki, Tyrer, Jonathan, Kote-Jarai, Zsofi A., Lawrenson, Kate, Lindstrom, Sara, Ramus, Susan J., Thompson, Deborah J., Kibel, Adam S., Dansonka-Mieszkowska, Agnieszka, Michael, Agnieszka, Dieffenbach, Aida K., Gentry-Maharaj, Aleksandra, Whittemore, Alice S., Wolk, Alicja, Monteiro, Alvaro, Peixoto, Ana, Kierzek, Andrzej, Cox, Angela, Rudolph, Anja, Gonzalez-Neira, Anna, Wu, Anna H., Lindblom, Annika, Swerdlow, Anthony, Ziogas, Argyrios, Ekici, Arif B., Burwinkel, Barbara, Karlan, Beth Y., Nordestgaard, Borge G., Blomqvist, Carl, Phelan, Catherine, McLean, Catriona, Pearce, Celeste Leigh, Vachon, Celine, Cybulski, Cezary, Slavov, Chavdar, Stegmaier, Christa, Maier, Christiane, Ambrosone, Christine B., Hogdall, Claus K., Teerlink, Craig C., Kang, Daehee, Tessier, Daniel C., Schaid, Daniel J., Stram, Daniel O., Cramer, Daniel W., Neal, David E., Eccles, Diana, Flesch-Janys, Dieter, Edwards, Digna R. Velez, Wokozorczyk, Dominika, Levine, Douglas A., Yannoukakos, Drakoulis, Sawyer, Elinor J., Bandera, Elisa V., Poole, Elizabeth M., Goode, Ellen L., Khusnutdinova, Elza, Hogdall, Estrid, Song, Fengju, Bruinsma, Fiona, Heitz, Florian, Modugno, Francesmary, Hamdy, Freddie C., Wiklund, Fredrik, Giles, Graham G., Olsson, Hakan, Wildiers, Hans, Ulmer, Hans-Ulrich, Pandha, Hardev, Risch, Harvey A., Darabi, Hatef, Salvesen, Helga B., Nevanlinna, Heli, Gronberg, Henrik, Brenner, Hermann, Brauch, Hiltrud, Anton-Culver, Hoda, Song, Honglin, Lim, Hui-Yi, McNeish, Iain, Campbell, Ian, Vergote, Ignace, Gronwald, Jacek, Lubinski, Jan, Stanford, Janet L., Bentez, Javier, Doherty, Jennifer A., Permuth, Jennifer B., Chang-Claude, Jenny, Donovan, Jenny L., Dennis, Joe, Schildkraut, Joellen M., Schleutker, Johanna, Hopper, John L., Kupryjanczyk, Jolanta, Park, Jong Y., Figueroa, Jonine, Clements, Judith A., Knight, Julia A., Peto, Julian, Cunningham, Julie M., Pow-Sang, Julio, Batra, Jyotsna, Czene, Kamila, Lu, Karen H., Herkommer, Kathleen, Khaw, Kay-Tee, Matsuo, Keitaro, Muir, Kenneth, Offitt, Kenneth, Chen, Kexin, Moysich, Kirsten B., Aittomaki, Kristiina, Odunsi, Kunle, Kiemeney, Lambertus A., Massuger, Leon F. A. G., Fitzgerald, Liesel M., Cook, Linda S., Cannon-Albright, Lisa, Hooning, Maartje J., Pike, Malcolm C., Bolla, Manjeet K., Luedeke, Manuel, Teixeira, Manuel R., Goodman, Marc T., Schmidt, Marjanka K., Riggan, Marjorie, Aly, Markus, Rossing, Mary Anne, Beckmann, Matthias W., Moisse, Matthieu, Sanderson, Maureen, Southey, Melissa C., Jones, Michael, Lush, Michael, Hildebrandt, Michelle A. T., Hou, Ming-Feng, Schoemaker, Minouk J., Garcia-Closas, Montserrat, Bogdanova, Natalia, Rahman, Nazneen, Le, Nhu D., Orr, Nick, Wentzensen, Nicolas, Pashayan, Nora, Peterlongo, Paolo, Guenel, Pascal, Brennan, Paul, Paulo, Paula, Webb, Penelope M., Broberg, Per, Fasching, Peter A., Devilee, Peter, Wang, Qin, Cai, Qiuyin, Li, Qiyuan, Kaneva, Radka, Butzow, Ralf, Kopperud, Reidun Kristin, Schmutzler, Rita K., Stephenson, Robert A., MacInnis, Robert J., Hoover, Robert N., Winqvist, Robert, Ness, Roberta, Milne, Roger L., Travis, Ruth C., Benlloch, Sara, Olson, Sara H., McDonnell, Shannon K., Tworoger, Shelley S., Maia, Sofi A., Berndt, Sonja, Lee, Soo Chin, Teo, Soo-Hwang, Thibodeau, Stephen N., Bojesen, Stig E., Gapstur, Susan M., Kjaer, Susanne Krueger, Pejovic, Tanja, Tammela, Teuvo L. J., Doerk, Thilo, Bruening, Thomas, Wahlfors, Tiina, Key, Tim J., Edwards, Todd L., Menon, Usha, Hamann, Ute, Mitev, Vanio, Kosma, Veli-Matti, Setiawan, Veronica Wendy, Kristensen, Vessela, Arndt, Volker, Vogel, Walther, Zheng, Wei, Sieh, Weiva, Blot, William J., Kluzniak, Wojciech, Shu, Xiao-Ou, Gao, Yu-Tang, Schumacher, Fredrick, Freedman, Matthew L., Berchuck, Andrew, Dunning, Alison M., Simard, Jacques, Haiman, Christopher A., Spurdle, Amanda, Sellers, Thomas A., Hunter, David J., Henderson, Brian E., Kraft, Peter, Chanock, Stephen J., Couch, Fergus J., Hall, Per, Gayther, Simon A., Easton, Douglas F., Chenevix-Trench, Georgia, Eeles, Rosalind, Pharoah, Paul D. P., and Lambrechts, Diether
Abstract: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10 -8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. (C) 2016 AACR.
Published: 2016
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13. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author: Spurdle, Amanda B., Couch, Fergus J., Parsons, Michael T., McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K., Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D. Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L., Domchek, Susan M., Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Ake, Andrulis, Irene L., Miron, Alexander, Hansen, Thomas V. O., Caldes, Trinidad, Neuhausen, Susan L., Toland, Amanda E., Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K., Osorio, Ana, Factor, Rachel E., Terry, Mary B., Rebbeck, Timothy R., Karlan, Beth Y., Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul D. P., Blows, Fiona M., Dunning, Alison M., Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K., Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Slamon, Dennis J., Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomaki, Kristiina, Muranen, Taru A., Heikkila, Paivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J., Brinton, Louise, Lissowska, Jolanta, Olson, Janet E., Pankratz, Vernon S., John, Esther M., Whittemore, Alice S., West, Dee W., Hamann, Ute, Torres, Diana, Ulmer, Hans Ulrich, Rudiger, Thomas, Devilee, Peter, Tollenaar, Robert A. E. M., Seynaeve, Caroline, Van Asperen, Christi J., Eccles, Diana M., Tapper, William J., Durcan, Lorraine, Jones, Louise, Peto, Julian, dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Dwek, Miriam, Swann, Ruth, Bane, Anita L., Glendon, Gord, Mulligan, Anna M., Giles, Graham G., Milne, Roger L., Baglietto, Laura, McLean, Catriona, Carpenter, Jane, Clarke, Christine, Scott, Rodney, Brauch, Hiltrud, Bruning, Thomas, Ko, Yon-Dschun, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Dork, Thilo, Bogdanova, Natalia, Park-Simon, Tjoung-Won, Hillemanns, Peter, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Burwinkel, Barbara, Marme, Frederik, Surovy, Harald, Yang, Rongxi, Anton-Culver, Hoda, Ziogas, Argyrios, Hooning, Maartje J., Collee, J. Margriet, Martens, John W. M., Tilanus-Linthorst, Madeleine M. A., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volke, Stegmaier, Christa, Winqvist, Robert, Pylkas, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Lindblom, Annika, Margolin, Sara, Joseph, Vijai, Robson, Mark, Rau-Murthy, Rohini, Gonzalez-Neira, Anna, Arias, Jose Ignacio, Zamora, Pilar, Benitez, Javier, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Peterlongo, Paolo, Zaffaroni, Daniela, Barile, Monica, Capra, Fabio, Radice, Paolo, Teo, Soo H., Easton, Douglas F., Antoniou, Antonis C., Chenevix-Trench, Georgia, Goldgar, David E., Spurdle, Amanda B., Couch, Fergus J., Parsons, Michael T., McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K., Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D. Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L., Domchek, Susan M., Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Ake, Andrulis, Irene L., Miron, Alexander, Hansen, Thomas V. O., Caldes, Trinidad, Neuhausen, Susan L., Toland, Amanda E., Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K., Osorio, Ana, Factor, Rachel E., Terry, Mary B., Rebbeck, Timothy R., Karlan, Beth Y., Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul D. P., Blows, Fiona M., Dunning, Alison M., Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K., Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Slamon, Dennis J., Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomaki, Kristiina, Muranen, Taru A., Heikkila, Paivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J., Brinton, Louise, Lissowska, Jolanta, Olson, Janet E., Pankratz, Vernon S., John, Esther M., Whittemore, Alice S., West, Dee W., Hamann, Ute, Torres, Diana, Ulmer, Hans Ulrich, Rudiger, Thomas, Devilee, Peter, Tollenaar, Robert A. E. M., Seynaeve, Caroline, Van Asperen, Christi J., Eccles, Diana M., Tapper, William J., Durcan, Lorraine, Jones, Louise, Peto, Julian, dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Dwek, Miriam, Swann, Ruth, Bane, Anita L., Glendon, Gord, Mulligan, Anna M., Giles, Graham G., Milne, Roger L., Baglietto, Laura, McLean, Catriona, Carpenter, Jane, Clarke, Christine, Scott, Rodney, Brauch, Hiltrud, Bruning, Thomas, Ko, Yon-Dschun, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Dork, Thilo, Bogdanova, Natalia, Park-Simon, Tjoung-Won, Hillemanns, Peter, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Burwinkel, Barbara, Marme, Frederik, Surovy, Harald, Yang, Rongxi, Anton-Culver, Hoda, Ziogas, Argyrios, Hooning, Maartje J., Collee, J. Margriet, Martens, John W. M., Tilanus-Linthorst, Madeleine M. A., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volke, Stegmaier, Christa, Winqvist, Robert, Pylkas, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Lindblom, Annika, Margolin, Sara, Joseph, Vijai, Robson, Mark, Rau-Murthy, Rohini, Gonzalez-Neira, Anna, Arias, Jose Ignacio, Zamora, Pilar, Benitez, Javier, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Peterlongo, Paolo, Zaffaroni, Daniela, Barile, Monica, Capra, Fabio, Radice, Paolo, Teo, Soo H., Easton, Douglas F., Antoniou, Antonis C., Chenevix-Trench, Georgia, and Goldgar, David E.
Abstract: Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. Results: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)
Published: 2014

14. The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity

Author: Colombo, Mara, Lòpez-Perolio, Irene, Meeks, Huong D, Caleca, Laura, Parsons, Michael, Li, Hongyan, De Vecchi, Giovanna, Tudini, Emma, Foglia, Claudia, Mondini, Patrizia, Manoukian, Siranoush, Behar, Raquel, Garcia, Encarna B Gomez, Meindl, Alfons, Montagna, Marco, Niederacher, Dieter, Schmidt, Ane Y, Varesco, Liliana, Wappenschmidt, Barbara, Bolla, Manjeet K, Dennis, Joe, Michailidou, Kyriaki, Wang, Qin, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Beckmann, Matthias W, Beeghly-Fadel, Alicia, Benitez, Javier, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Chang-Claude, Jenny, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Eriksson, Mikael, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Gabrielson, Marike, García-Closas, Montserrat, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Hartman, Mikael, Hauke, Jan, Hollestelle, Antoinette, Hopper, John L, Jakubowska, Anna, Jung, Audrey, Kosma, Veli-Matti, Lambrechts, Diether, Marchand, Loic Le, Lindblom, Annika, Lubinski, Jan, Mannermaa, Arto, Margolin, Sara, Miao, Hui, Milne, Roger L, Neuhausen, Susan L, Nevanlinna, Heli, Olson, Janet E, Peterlongo, Paolo, Peto, Julian, Pylkäs, Katri, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Schneeweiss, Andreas, Schoemaker, Minouk J, See, Mee Hoong, Southey, Melissa C, Swerdlow, Anthony, Teo, Soo H, Toland, Amanda E, Tomlinson, Ian, Truong, Thérèse, van Asperen, Christi J, van den Ouweland, Ans MW, van der Kolk, Lizet, Winqvist, Robert, Yannoukakos, Drakoulis, Zheng, Wei, Dunning, Alison M, Easton, Douglas F, Henderson, Alex, Hogervorst, Frans, Izatt, Louise, Offitt, Kenneth, Side, Lucy E, van Rensburg, Elizabeth J, Embrace, Study, Hebon, Study, McGuffog, Lesley, Antoniou, Antonis C, Chenevix-Trench, Georgia, Spurdle, Amanda B, Goldgar, David E, de la Hoya, Miguel, and Radice, Paolo
Subjects: BRCA2 Protein, Base Sequence, Models, Genetic, digital PCR, multifactorial likelihood analysis, spliceogenic variants, Mitomycin, RNA Splicing, Genetic Variation, Exons, BRCA2, Cell Line, Calibration, Humans, Female, Genetic Predisposition to Disease, quantitative real-time PCR, RNA, Messenger
Abstract: Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10. There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24), nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the non-pathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants. This article is protected by copyright. All rights reserved. ispartof: Human Mutation vol:39 issue:5 pages:729-741 ispartof: location:United States status: published
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15. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Kar, Siddhartha P, Beesley, Jonathan, Amin Al Olama, Ali, Michailidou, Kyriaki, Tyrer, Jonathan, Kote-Jarai, ZSofia, Lawrenson, Kate, Lindstrom, Sara, Ramus, Susan J, Thompson, Deborah J, ABCTB Investigators, Kibel, Adam S, Dansonka-Mieszkowska, Agnieszka, Michael, Agnieszka, Dieffenbach, Aida K, Gentry-Maharaj, Aleksandra, Whittemore, Alice S, Wolk, Alicja, Monteiro, Alvaro, Peixoto, Ana, Kierzek, Andrzej, Cox, Angela, Rudolph, Anja, Gonzalez-Neira, Anna, Wu, Anna H, Lindblom, Annika, Swerdlow, Anthony, AOCS Study Group & Australian Cancer Study (Ovarian Cancer), APCB BioResource, Ziogas, Argyrios, Ekici, Arif B, Burwinkel, Barbara, Karlan, Beth Y, Nordestgaard, Børge G, Blomqvist, Carl, Phelan, Catherine, McLean, Catriona, Pearce, Celeste Leigh, Vachon, Celine, Cybulski, Cezary, Slavov, Chavdar, Stegmaier, Christa, Maier, Christiane, Ambrosone, Christine B, Høgdall, Claus K, Teerlink, Craig C, Kang, Daehee, Tessier, Daniel C, Schaid, Daniel J, Stram, Daniel O, Cramer, Daniel W, Neal, David E, Eccles, Diana, Flesch-Janys, Dieter, Edwards, Digna R Velez, Wokozorczyk, Dominika, Levine, Douglas A, Yannoukakos, Drakoulis, Sawyer, Elinor J, Bandera, Elisa V, Poole, Elizabeth M, Goode, Ellen L, Khusnutdinova, Elza, Høgdall, Estrid, Song, Fengju, Bruinsma, Fiona, Heitz, Florian, Modugno, Francesmary, Hamdy, Freddie C, Wiklund, Fredrik, Giles, Graham G, Olsson, Håkan, Wildiers, Hans, Ulmer, Hans-Ulrich, Pandha, Hardev, Risch, Harvey A, Darabi, Hatef, Salvesen, Helga B, Nevanlinna, Heli, Gronberg, Henrik, Brenner, Hermann, Brauch, Hiltrud, Anton-Culver, Hoda, Song, Honglin, Lim, Hui-Yi, McNeish, Iain, Campbell, Ian, Vergote, Ignace, Gronwald, Jacek, Lubiński, Jan, Stanford, Janet L, Benítez, Javier, Doherty, Jennifer A, Permuth, Jennifer B, Chang-Claude, Jenny, Donovan, Jenny L, Dennis, Joe, Schildkraut, Joellen M, Schleutker, Johanna, Hopper, John L, Kupryjanczyk, Jolanta, Park, Jong Y, Figueroa, Jonine, Clements, Judith A, Knight, Julia A, Peto, Julian, Cunningham, Julie M, Pow-Sang, Julio, Batra, Jyotsna, Czene, Kamila, Lu, Karen H, Herkommer, Kathleen, Khaw, Kay-Tee, KConFab Investigators, Matsuo, Keitaro, Muir, Kenneth, Offitt, Kenneth, Chen, Kexin, Moysich, Kirsten B, Aittomäki, Kristiina, Odunsi, Kunle, Kiemeney, Lambertus A, Massuger, Leon FAG, Fitzgerald, Liesel M, Cook, Linda S, Cannon-Albright, Lisa, Hooning, Maartje J, Pike, Malcolm C, Bolla, Manjeet K, Luedeke, Manuel, Teixeira, Manuel R, Goodman, Marc T, Schmidt, Marjanka K, Riggan, Marjorie, Aly, Markus, Rossing, Mary Anne, Beckmann, Matthias W, Moisse, Matthieu, Sanderson, Maureen, Southey, Melissa C, Jones, Michael, Lush, Michael, Hildebrandt, Michelle AT, Hou, Ming-Feng, Schoemaker, Minouk J, Garcia-Closas, Montserrat, Bogdanova, Natalia, Rahman, Nazneen, NBCS Investigators, Le, Nhu D, Orr, Nick, Wentzensen, Nicolas, Pashayan, Nora, Peterlongo, Paolo, Guénel, Pascal, Brennan, Paul, Paulo, Paula, Webb, Penelope M, Broberg, Per, Fasching, Peter A, Devilee, Peter, Wang, Qin, Cai, Qiuyin, Li, Qiyuan, Kaneva, Radka, Butzow, Ralf, Kopperud, Reidun Kristin, Schmutzler, Rita K, Stephenson, Robert A, MacInnis, Robert J, Hoover, Robert N, Winqvist, Robert, Ness, Roberta, Milne, Roger L, Travis, Ruth C, Benlloch, Sara, Olson, Sara H, McDonnell, Shannon K, Tworoger, Shelley S, Maia, Sofia, Berndt, Sonja, Lee, Soo Chin, Teo, Soo-Hwang, Thibodeau, Stephen N, Bojesen, Stig E, Gapstur, Susan M, Kjær, Susanne Krüger, Pejovic, Tanja, Tammela, Teuvo LJ, GENICA Network, PRACTICAL Consortium, Dörk, Thilo, Brüning, Thomas, Wahlfors, Tiina, Key, Tim J, Edwards, Todd L, Menon, Usha, Hamann, Ute, Mitev, Vanio, Kosma, Veli-Matti, Setiawan, Veronica Wendy, Kristensen, Vessela, Arndt, Volker, Vogel, Walther, Zheng, Wei, Sieh, Weiva, Blot, William J, Kluzniak, Wojciech, Shu, Xiao-Ou, Gao, Yu-Tang, Schumacher, Fredrick, Freedman, Matthew L, Berchuck, Andrew, Dunning, Alison M, Simard, Jacques, Haiman, Christopher A, Spurdle, Amanda, Sellers, Thomas A, Hunter, David J, Henderson, Brian E, Kraft, Peter, Chanock, Stephen J, Couch, Fergus J, Hall, Per, Gayther, Simon A, Easton, Douglas F, Chenevix-Trench, Georgia, Eeles, Rosalind, Pharoah, Paul DP, and Lambrechts, Diether
Subjects: Male, Ovarian Neoplasms, Quantitative Trait Loci, Chromosome Mapping, Datasets as Topic, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, 3. Good health, Enhancer Elements, Genetic, Meta-Analysis as Topic, Genetic Loci, Organ Specificity, Case-Control Studies, Humans, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Signal Transduction
Abstract: UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

16. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

Author: Wang, Xiaoliang, Dai, James Y, Albanes, Demetrius, Arndt, Volker, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Buchanan, Daniel D, Butterbach, Katja, Caan, Bette, Casey, Graham, Campbell, Peter T, Chan, Andrew T, Chen, Zhengyi, Chang-Claude, Jenny, Cotterchio, Michelle, Easton, Douglas F, Giles, Graham G, Giovannucci, Edward, Grady, William M, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Jenkins, Mark A, Joshi, Amit D, Lampe, Johanna W, Larsson, Susanna C, Lejbkowicz, Flavio, Li, Li, Lindblom, Annika, Le Marchand, Loic, Martin, Vicente, Milne, Roger L, Moreno, Victor, Newcomb, Polly A, Offitt, Kenneth, Ogino, Shuji, Pharoah, Paul DP, Pinchev, Mila, Potter, John D, Rennert, Hedy S, Rennert, Gad, Saliba, Walid, Schafmayer, Clemens, Schoen, Robert E, Schrotz-King, Petra, Slattery, Martha L, Song, Mingyang, Stegmaier, Christa, Weinstein, Stephanie J, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Gruber, Stephen B, Peters, Ulrike, and White, Emily
Subjects: Male, colorectal cancer, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, 3. Good health, C-reactive protein, Causality, Logistic Models, Mendelian randomization, Humans, epidemiology, Female, Genetic Predisposition to Disease, Colorectal Neoplasms, Aged
Abstract: BACKGROUND: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. METHODS: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. RESULTS: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. CONCLUSIONS: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.

17. Refined histopathological predictors of BRCA1 and BRCA2 mutation status : a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author: Pontificia Universidad Javeriana. Facultad de Medicina. Instituto de Genética Humana, Spurdle, Amanda B., Couch, Fergus J., Parsons, Michael T., McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K., Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D. Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L., Domchek, Susan M., Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Ake, Andrulis, Irene L., Miron, Alexander, Hansen, Thomas V. O., Caldes, Trinidad, Neuhausen, Susan L., Toland, Amanda E., Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K., Osorio, Ana, Factor, Rachel E., Terry, Mary B., Rebbeck, Timothy R., Karlan, Beth Y., Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul D. P., Blows, Fiona M., Dunning, Alison M., Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K., Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Slamon, Dennis J., Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomäki, Kristiina, Muranen, Taru A., Heikkilä, Päivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J., Brinton, Louise, Lissowska, Jolanta, Olson, Janet E., Pankratz, Vernon S., John, Esther M., Whittemore, Alice S., West, Dee W., Hamann, Ute, Torres López, Diana María, Ulmer, Hans Ulrich, Rüdiger, Thomas, Devilee, Peter, Tollenaar, Robert A. E. M, Seynaeve, Caroline, Van Asperen, Christi J., Eccles, Diana M., Tapper, William J., Durcan, Lorraine, Jones, Louise, Peto, Julian, dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Dwek, Miriam, Swann, Ruth, Bane, Anita L., Glendon, Gord, Mulligan, Anna M., Giles, Graham G., Milne, Roger L., Baglietto, Laura, McLean, Catriona, Carpenter, Jane, Clarke, Christine, Scott, Rodney, Brauch, Hiltrud, Brüning, Thomas, Ko, Yon-Dschun, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Dörk, Thilo, Bogdanova, Natalia, Park-Simon, Tjoung-Won, Hillemanns, Peter, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Burwinkel, Barbara, Marme, Frederik, Surovy, Harald, Yang, Rongxi, Anton-Culver, Hoda, Ziogas, Argyrios, Hooning, Maartje J., Collée, J. Margriet, Martens, John W. M., Tilanus-Linthorst, Madeleine M. A., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volke, Stegmaier, Christa, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Lindblom, Annika, Margolin, Sara, Joseph, Vijai, Robson, Mark, Rau-Murthy, Rohini, González Neira, Anna, Arias, Jose Ignacio, Zamora, Pilar, Benítez, Javier, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Peterlongo, Paolo, Zaffaroni, Daniela, Barile, Monica, Capra, Fabio, Radice, Paolo, Teo, Soo H., Easton, Douglas F., Antoniou, Antonis C., Chenevix-Trench, Georgia, Goldgar, David E., Pontificia Universidad Javeriana. Facultad de Medicina. Instituto de Genética Humana, Spurdle, Amanda B., Couch, Fergus J., Parsons, Michael T., McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K., Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D. Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L., Domchek, Susan M., Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Ake, Andrulis, Irene L., Miron, Alexander, Hansen, Thomas V. O., Caldes, Trinidad, Neuhausen, Susan L., Toland, Amanda E., Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K., Osorio, Ana, Factor, Rachel E., Terry, Mary B., Rebbeck, Timothy R., Karlan, Beth Y., Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul D. P., Blows, Fiona M., Dunning, Alison M., Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K., Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A., Beckmann, Matthias W., Ekici, Arif B., Slamon, Dennis J., Bojesen, Stig E., Nordestgaard, Borge G., Nielsen, Sune F., Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomäki, Kristiina, Muranen, Taru A., Heikkilä, Päivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J., Brinton, Louise, Lissowska, Jolanta, Olson, Janet E., Pankratz, Vernon S., John, Esther M., Whittemore, Alice S., West, Dee W., Hamann, Ute, Torres López, Diana María, Ulmer, Hans Ulrich, Rüdiger, Thomas, Devilee, Peter, Tollenaar, Robert A. E. M, Seynaeve, Caroline, Van Asperen, Christi J., Eccles, Diana M., Tapper, William J., Durcan, Lorraine, Jones, Louise, Peto, Julian, dos-Santos-Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Dwek, Miriam, Swann, Ruth, Bane, Anita L., Glendon, Gord, Mulligan, Anna M., Giles, Graham G., Milne, Roger L., Baglietto, Laura, McLean, Catriona, Carpenter, Jane, Clarke, Christine, Scott, Rodney, Brauch, Hiltrud, Brüning, Thomas, Ko, Yon-Dschun, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Dörk, Thilo, Bogdanova, Natalia, Park-Simon, Tjoung-Won, Hillemanns, Peter, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Burwinkel, Barbara, Marme, Frederik, Surovy, Harald, Yang, Rongxi, Anton-Culver, Hoda, Ziogas, Argyrios, Hooning, Maartje J., Collée, J. Margriet, Martens, John W. M., Tilanus-Linthorst, Madeleine M. A., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volke, Stegmaier, Christa, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Lindblom, Annika, Margolin, Sara, Joseph, Vijai, Robson, Mark, Rau-Murthy, Rohini, González Neira, Anna, Arias, Jose Ignacio, Zamora, Pilar, Benítez, Javier, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Peterlongo, Paolo, Zaffaroni, Daniela, Barile, Monica, Capra, Fabio, Radice, Paolo, Teo, Soo H., Easton, Douglas F., Antoniou, Antonis C., Chenevix-Trench, Georgia, and Goldgar, David E.

18. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk.

Author: Wang X, Dai JY, Albanes D, Arndt V, Berndt SI, Bézieau S, Brenner H, Buchanan DD, Butterbach K, Caan B, Casey G, Campbell PT, Chan AT, Chen Z, Chang-Claude J, Cotterchio M, Easton DF, Giles GG, Giovannucci E, Grady WM, Hoffmeister M, Hopper JL, Hsu L, Jenkins MA, Joshi AD, Lampe JW, Larsson SC, Lejbkowicz F, Li L, Lindblom A, Le Marchand L, Martin V, Milne RL, Moreno V, Newcomb PA, Offitt K, Ogino S, Pharoah PDP, Pinchev M, Potter JD, Rennert HS, Rennert G, Saliba W, Schafmayer C, Schoen RE, Schrotz-King P, Slattery ML, Song M, Stegmaier C, Weinstein SJ, Wolk A, Woods MO, Wu AH, Gruber SB, Peters U, and White E
Subjects: Aged, C-Reactive Protein genetics, Causality, Colorectal Neoplasms genetics, Female, Genetic Predisposition to Disease, Humans, Logistic Models, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, C-Reactive Protein metabolism, Colorectal Neoplasms epidemiology
Abstract: Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach., Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk., Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors., Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development., (© The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)
Published: 2019
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19. The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity.

Author: Colombo M, Lòpez-Perolio I, Meeks HD, Caleca L, Parsons MT, Li H, De Vecchi G, Tudini E, Foglia C, Mondini P, Manoukian S, Behar R, Garcia EBG, Meindl A, Montagna M, Niederacher D, Schmidt AY, Varesco L, Wappenschmidt B, Bolla MK, Dennis J, Michailidou K, Wang Q, Aittomäki K, Andrulis IL, Anton-Culver H, Arndt V, Beckmann MW, Beeghly-Fadel A, Benitez J, Boeckx B, Bogdanova NV, Bojesen SE, Bonanni B, Brauch H, Brenner H, Burwinkel B, Chang-Claude J, Conroy DM, Couch FJ, Cox A, Cross SS, Czene K, Devilee P, Dörk T, Eriksson M, Fasching PA, Figueroa J, Fletcher O, Flyger H, Gabrielson M, García-Closas M, Giles GG, González-Neira A, Guénel P, Haiman CA, Hall P, Hamann U, Hartman M, Hauke J, Hollestelle A, Hopper JL, Jakubowska A, Jung A, Kosma VM, Lambrechts D, Le Marchand L, Lindblom A, Lubinski J, Mannermaa A, Margolin S, Miao H, Milne RL, Neuhausen SL, Nevanlinna H, Olson JE, Peterlongo P, Peto J, Pylkäs K, Sawyer EJ, Schmidt MK, Schmutzler RK, Schneeweiss A, Schoemaker MJ, See MH, Southey MC, Swerdlow A, Teo SH, Toland AE, Tomlinson I, Truong T, van Asperen CJ, van den Ouweland AMW, van der Kolk LE, Winqvist R, Yannoukakos D, Zheng W, Dunning AM, Easton DF, Henderson A, Hogervorst FBL, Izatt L, Offitt K, Side LE, van Rensburg EJ, Embrace S, Hebon S, McGuffog L, Antoniou AC, Chenevix-Trench G, Spurdle AB, Goldgar DE, Hoya M, and Radice P
Subjects: BRCA2 Protein metabolism, Base Sequence, Calibration, Cell Line, Exons genetics, Female, Genetic Predisposition to Disease, Humans, Mitomycin pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, BRCA2 Protein genetics, Genetic Variation, Models, Genetic, RNA Splicing genetics
Abstract: Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10 -115 . There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants., (© 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.)
Published: 2018
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20. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

Author: Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, Lawrenson K, Lindstrom S, Ramus SJ, Thompson DJ, Kibel AS, Dansonka-Mieszkowska A, Michael A, Dieffenbach AK, Gentry-Maharaj A, Whittemore AS, Wolk A, Monteiro A, Peixoto A, Kierzek A, Cox A, Rudolph A, Gonzalez-Neira A, Wu AH, Lindblom A, Swerdlow A, Ziogas A, Ekici AB, Burwinkel B, Karlan BY, Nordestgaard BG, Blomqvist C, Phelan C, McLean C, Pearce CL, Vachon C, Cybulski C, Slavov C, Stegmaier C, Maier C, Ambrosone CB, Høgdall CK, Teerlink CC, Kang D, Tessier DC, Schaid DJ, Stram DO, Cramer DW, Neal DE, Eccles D, Flesch-Janys D, Edwards DR, Wokozorczyk D, Levine DA, Yannoukakos D, Sawyer EJ, Bandera EV, Poole EM, Goode EL, Khusnutdinova E, Høgdall E, Song F, Bruinsma F, Heitz F, Modugno F, Hamdy FC, Wiklund F, Giles GG, Olsson H, Wildiers H, Ulmer HU, Pandha H, Risch HA, Darabi H, Salvesen HB, Nevanlinna H, Gronberg H, Brenner H, Brauch H, Anton-Culver H, Song H, Lim HY, McNeish I, Campbell I, Vergote I, Gronwald J, Lubiński J, Stanford JL, Benítez J, Doherty JA, Permuth JB, Chang-Claude J, Donovan JL, Dennis J, Schildkraut JM, Schleutker J, Hopper JL, Kupryjanczyk J, Park JY, Figueroa J, Clements JA, Knight JA, Peto J, Cunningham JM, Pow-Sang J, Batra J, Czene K, Lu KH, Herkommer K, Khaw KT, Matsuo K, Muir K, Offitt K, Chen K, Moysich KB, Aittomäki K, Odunsi K, Kiemeney LA, Massuger LF, Fitzgerald LM, Cook LS, Cannon-Albright L, Hooning MJ, Pike MC, Bolla MK, Luedeke M, Teixeira MR, Goodman MT, Schmidt MK, Riggan M, Aly M, Rossing MA, Beckmann MW, Moisse M, Sanderson M, Southey MC, Jones M, Lush M, Hildebrandt MA, Hou MF, Schoemaker MJ, Garcia-Closas M, Bogdanova N, Rahman N, Le ND, Orr N, Wentzensen N, Pashayan N, Peterlongo P, Guénel P, Brennan P, Paulo P, Webb PM, Broberg P, Fasching PA, Devilee P, Wang Q, Cai Q, Li Q, Kaneva R, Butzow R, Kopperud RK, Schmutzler RK, Stephenson RA, MacInnis RJ, Hoover RN, Winqvist R, Ness R, Milne RL, Travis RC, Benlloch S, Olson SH, McDonnell SK, Tworoger SS, Maia S, Berndt S, Lee SC, Teo SH, Thibodeau SN, Bojesen SE, Gapstur SM, Kjær SK, Pejovic T, Tammela TL, Dörk T, Brüning T, Wahlfors T, Key TJ, Edwards TL, Menon U, Hamann U, Mitev V, Kosma VM, Setiawan VW, Kristensen V, Arndt V, Vogel W, Zheng W, Sieh W, Blot WJ, Kluzniak W, Shu XO, Gao YT, Schumacher F, Freedman ML, Berchuck A, Dunning AM, Simard J, Haiman CA, Spurdle A, Sellers TA, Hunter DJ, Henderson BE, Kraft P, Chanock SJ, Couch FJ, Hall P, Gayther SA, Easton DF, Chenevix-Trench G, Eeles R, Pharoah PD, and Lambrechts D
Subjects: Breast Neoplasms metabolism, Case-Control Studies, Chromosome Mapping, Datasets as Topic, Enhancer Elements, Genetic, Female, Gene Regulatory Networks, Humans, Male, Meta-Analysis as Topic, Organ Specificity genetics, Polymorphism, Single Nucleotide, Prostatic Neoplasms metabolism, Quantitative Trait Loci, Signal Transduction, Breast Neoplasms genetics, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Ovarian Neoplasms genetics, Prostatic Neoplasms genetics
Abstract: Unlabelled: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis., Significance: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932., Competing Interests: The authors disclose no potential conflicts of interest., (©2016 American Association for Cancer Research.)
Published: 2016
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20 results on '"Offitt, Kenneth"'

1. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.

2. Refined histopathological predictors of BRCA1 and BRCA2mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

3. Supplementary Methods, Figures S1 - S3 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

4. Supplementary Tables S1 - S10 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

5. Supplementary Acknowledgments from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

6. Data from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

7. Supplementary Grant Support from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

8. Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies

9. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

10. The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity

11. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

12. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

13. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

14. The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity

15. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

16. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

17. Refined histopathological predictors of BRCA1 and BRCA2 mutation status : a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

18. Mendelian randomization analysis of C-reactive protein on colorectal cancer risk.

19. The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity.

20. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

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