Author: "German Cancer Research Center (DKFZ)" - Searchworks@Jio Institute Digital Library Search Results

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14,688 results on '"German Cancer Research Center (DKFZ)"'

1. High-resolution pulmonary arterio- and venography using multiple-bolus multiphase 3D-gd-mRA

Author: Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109. ; Department of Radiology, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany. ; Department of Radiology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109., Department of Radiology, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany., Department of Neurology, University Hospitals, 69120 Heidelberg, Germany., Siemens Medical Systems, 91052 Erlangen, Germany., Schoenberg, Stefan O., Bock, Michael, Floemer, Frank, Grau, Armin, Williams, David M., Laub, Gerhard, Knopp, Michael V., Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109. ; Department of Radiology, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany. ; Department of Radiology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany., Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109., Department of Radiology, German Cancer Research Center (dkfz), 69120 Heidelberg, Germany., Department of Neurology, University Hospitals, 69120 Heidelberg, Germany., Siemens Medical Systems, 91052 Erlangen, Germany., Schoenberg, Stefan O., Bock, Michael, Floemer, Frank, Grau, Armin, Williams, David M., Laub, Gerhard, and Knopp, Michael V.
Abstract: The purpose of this study was to demonstrate selective visualization of pulmonary arteries and veins with high spatial resolution for improved detection of vascular pathologies. Time-resolved pulmonary three-dimensional gadolinium-enhanced magnetic resonance angiograms (3D-Gd-MRA) were acquired with an ultrashort 3D fast low-angle shot (FLASH) sequence (TR/TE 2.3/0.9 msec) using asymmetric k-space sampling in readout, phase-encoding, and partition directions. In a single breath-hold four consecutive acquisitions were performed with a scan time of 6.28 seconds for each phase. A spatial resolution of 1.9 × 1.4 × 2 mm 3 could be achieved for a 12 cm thick 3D volume. To exploit the intrinsic enhancement kinetics of the pulmonary vascular system, the infusion of two gadolinium chelate boli was synchronized with the acquisition of the first and third data sets. This infusion strategy created two predominantly pulmonary arterial and venous data sets with the arterial and venous signal being maximally anti-correlated in time. A further separation of arterial and venous signal could be achieved by means of a correlation analysis. Eight patients with suspected thrombi in the pulmonary veins were studied. The calculated correlation angiographies provided high-quality pulmonary arterio- and venograms. Background signal was completely eliminated, allowing maximum intensity projection analysis of the full data set. In 7/8 patients no venous contamination of the arterial phase and vice versa was found. Patency of the pulmonary arteries and veins could be reliably assessed to the level of the segmental vessels. The combination of ultrafast multiphase 3D-Gd-MRA and dual-bolus injection with a correlation analysis of vascular signal provides high-resolution pulmonary arterio- and venograms. This imaging strategy initiates a new competitor to X-ray angiography. J. Magn. Reson. Imaging 1999;10:339-346. © 1999 Wiley-Liss, Inc.
Published: 2006

2. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author: [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, Rantala, Johanna, [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, and Rantala, Johanna
Abstract: To access publisher's full text version of this article click on the hyperlink below, The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

3. Quantification and reduction of cross-vendor variation in multicenter DWI MR imaging: results of the Cancer Core Europe imaging task force

Author: Oliver Lukas, Sedlaczek, Jens, Kleesiek, Ferdia A, Gallagher, Jacob, Murray, Sebastian, Prinz, Raquel, Perez-Lopez, Evia, Sala, Caroline, Caramella, Sebastian, Diffetock, Nathalie, Lassau, Andrew N, Priest, Chikako, Suzuki, Roberto, Vargas, Tommaso, Giandini, Marta, Vaiani, Antonella, Messina, Lennart K, Blomqvist, Regina G H, Beets-Tan, Petra, Oberrauch, Heinz-Peter, Schlemmer, Michael, Bach, Institut Català de la Salut, [Sedlaczek OL] Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Translational Medical Oncology, National Center for Tumor Diseases Heidelberg (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany. Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany. [Kleesiek J, Murray J, Prinz S] Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Gallagher FA] Department of Radiology, University of Cambridge, Cambridge, UK. [Perez-Lopez R] Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Phantoms, Imaging, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging::Diffusion Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Reproducibility of Results, Otros calificadores::Otros calificadores::/diagnóstico por imagen [Otros calificadores], General Medicine, Magnetic Resonance Imaging, Neoplasms [DISEASES], neoplasias [ENFERMEDADES], Europe, Diffusion Magnetic Resonance Imaging, Neoplasms, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética::imagen de resonancia magnética de difusión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Humans, Radiology, Nuclear Medicine and imaging, Càncer - Imatgeria per ressonància magnètica, Other subheadings::Other subheadings::/diagnostic imaging [Other subheadings]
Abstract: Objectives In the Cancer Core Europe Consortium (CCE), standardized biomarkers are required for therapy monitoring oncologic multicenter clinical trials. Multiparametric functional MRI and particularly diffusion-weighted MRI offer evident advantages for noninvasive characterization of tumor viability compared to CT and RECIST. A quantification of the inter- and intraindividual variation occurring in this setting using different hardware is missing. In this study, the MRI protocol including DWI was standardized and the residual variability of measurement parameters quantified. Methods Phantom and volunteer measurements (single-shot T2w and DW-EPI) were performed at the seven CCE sites using the MR hardware produced by three different vendors. Repeated measurements were performed at the sites and across the sites including a traveling volunteer, comparing qualitative and quantitative ROI-based results including an explorative radiomics analysis. Results For DWI/ADC phantom measurements using a central post-processing algorithm, the maximum deviation could be decreased to 2%. However, there is no significant difference compared to a decentralized ADC value calculation at the respective MRI devices. In volunteers, the measurement variation in 2 repeated scans did not exceed 11% for ADC and is below 20% for single-shot T2w in systematic liver ROIs. The measurement variation between sites amounted to 20% for ADC and < 25% for single-shot T2w. Explorative radiomics classification experiments yield better results for ADC than for single-shot T2w. Conclusion Harmonization of MR acquisition and post-processing parameters results in acceptable standard deviations for MR/DW imaging. MRI could be the tool in oncologic multicenter trials to overcome the limitations of RECIST-based response evaluation. Key Points • Harmonizing acquisition parameters and post-processing homogenization, standardized protocols result in acceptable standard deviations for multicenter MR–DWI studies. • Total measurement variation does not to exceed 11% for ADC in repeated measurements in repeated MR acquisitions, and below 20% for an identical volunteer travelling between sites. • Radiomic classification experiments were able to identify stable features allowing for reliable discrimination of different physiological tissue samples, even when using heterogeneous imaging data.
Published: 2022
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4. Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort

Author: Mathilde His, Vivian Viallon, Laure Dossus, Julie A. Schmidt, Ruth C. Travis, Marc J. Gunter, Kim Overvad, Cecilie Kyrø, Anne Tjønneland, Lucie Lécuyer, Joseph A. Rothwell, Gianluca Severi, Theron Johnson, Verena Katzke, Matthias B. Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Rosario Tumino, Alessandra Macciotta, Jolanda M. A. Boer, Evelyn M. Monninkhof, Karina Standahl Olsen, Therese H. Nøst, Torkjel M. Sandanger, Antonio Agudo, Maria-Jose Sánchez, Pilar Amiano, Sandra M. Colorado-Yohar, Eva Ardanaz, Linda Vidman, Anna Winkvist, Alicia K. Heath, Elisabete Weiderpass, Inge Huybrechts, Sabina Rinaldi, International Agency for Cancer Research (IACR), University of Oxford, Aarhus University [Aarhus], Danish Cancer Society Research Center [Copenhagen, Denmark] (DCSRC), University of Copenhagen = Københavns Universitet (UCPH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Firenze = University of Florence (UniFI), Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke [Nuthetal, Germany] (GIHNP-R), University of Potsdam = Universität Potsdam, Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), IRCCS Istituto Nazionale dei Tumori [Milano], University of Naples Federico II = Università degli studi di Napoli Federico II, Provincial Health Authority (ASP 7) [Ragusa, Italy], Università degli studi di Torino = University of Turin (UNITO), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University Medical Center [Utrecht], The Arctic University of Norway [Tromsø, Norway] (UiT), Catalan Institute of Oncology [Barcelone, Espagne], L’Hospitalet de Llobregat [Barcelona, Spain], Escuela Andaluza de Salud Pública [Granada, Spain] (EASP), Universidad de Granada = University of Granada (UGR), CIBER de Epidemiología y Salud Pública (CIBERESP), Public Health Division of Gipuzkoa, Basque Government, CIBER en Salud Pública, CIBERSP, Biodonostia Health Research Institute [Donostia-San Sebastian, Spain] (IIS Biodonostia), Murcia Regional Health Council [Murcia], Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Navarra Public Health Institute, Umeå University, Imperial College London, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Cancer Research UK, CRUK, World Cancer Research Fund, WCRF, University of Cambridge, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2015-166, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk (DOI 10.22025/2019.10.105.00004), C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143, MR/N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). The funders were not involved in designing the study, collecting, analyzing, or interpreting the data, or writing or submitting the manuscript for publication., The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., This work was funded by the French National Cancer Institute (grant number 2015-166). Mathilde His’ work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC., The authors would like to thank Mr Bertrand Hemon for his support in preparing the databases, Ms Audrey Gicquiau and Dr David Achaintre for the analyses of samples in several of the original studies, and all EPIC participants. The EPIC-Norfolk team thank all the participants who have been part of the project and the many members of the study teams at the University of Cambridge who have enabled this research. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., and HAL UVSQ, Équipe
Subjects: cross-sectional, lifestyle, Estils de vida, BIOMARKERS, Lifestyles, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, DIET, SERUM, Càncer de mama, Cohort Studies, Medicine, General & Internal, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Cross-sectional, General & Internal Medicine, Metabolites, Humans, Metabolomics, Prospective Studies, VALIDITY, Life Style, 11 Medical and Health Sciences, metabolites, RISK, Cancer och onkologi, Science & Technology, anthropometry, Anthropometry, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, PROFILES, Lifestyle, AMINO-ACID, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, PHYSICAL-ACTIVITY, Cross-Sectional Studies, Metabolòmica, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cancer and Oncology, TARGETED METABOLOMICS, Medicine, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Life Sciences & Biomedicine, Research Article
Abstract: This work was funded by the French National Cancer Institute (grant number 2015-166). Mathilde His' work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk (DOI 10.22025/2019.10.105.00004); C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143, MR/N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (UK). The funders were not involved in designing the study; collecting, analyzing, or interpreting the data; or writing or submitting the manuscript for publication., Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34: 2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated., Institut National du Cancer (INCA) France 2015-166, International Agency for Research on Cancer - Fondation ARC, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/1 MR/M012190/1
Published: 2021
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5. GWAS-Identified Variants for Obesity Do Not Influence the Risk of Developing Multiple Myeloma: A Population-Based Study and Meta-Analysis

Author: José Manuel Sánchez-Maldonado, Antonio José Cabrera-Serrano, Subhayan Chattopadhyay, Daniele Campa, María del Pilar Garrido, Angelica Macauda, Rob Ter Horst, Andrés Jerez, Mihai G. Netea, Yang Li, Kari Hemminki, Federico Canzian, Asta Försti, Juan Sainz, Institut Català de la Salut, [Sánchez-Maldonado JM, Cabrera-Serrano AJ] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain. [Chattopadhyay S] Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany. [Campa D] Department of Biology, University of Pisa, Pisa, Italy. [Garrido MDP] Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Macauda A] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jerez A] Experimental Hematology Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Genetic variants, Organic Chemistry, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], Mieloma múltiple - Aspectes genètics, Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight::Obesity [DISEASES], Obesitat - Complicacions, Hemic and Lymphatic Diseases::Hematologic Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Hemorrhagic Disorders::Hemostatic Disorders::Multiple Myeloma [DISEASES], General Medicine, Catalysis, Computer Science Applications, enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos hemorrágicos::trastornos hemostáticos::mieloma múltiple [ENFERMEDADES], Inorganic Chemistry, All institutes and research themes of the Radboud University Medical Center, Multiple myeloma, Susceptibility, afecciones patológicas, signos y síntomas::signos y síntomas::peso corporal::sobrepeso::obesidad [ENFERMEDADES], Obesity, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS]
Abstract: Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls). Results were then validated through meta-analysis with data from the UKBiobank (554 MM cases and 402,714 controls) and FinnGen cohorts (914 MM cases and 248,695 controls). Finally, we evaluated the correlation of these single nucleotide polymorphisms (SNPs) with cQTL data, serum inflammatory proteins, steroid hormones, and absolute numbers of blood-derived cell populations (n = 520). The meta-analysis of the four European cohorts showed no effect of obesity-related variants on the risk of developing MM. We only found a very modest association of the POC5rs2112347G and ADCY3rs11676272G alleles with MM risk that did not remain significant after correction for multiple testing (per-allele OR = 1.08, p = 0.0083 and per-allele OR = 1.06, p = 0.046). No correlation between these SNPs and functional data was found, which confirms that obesity-related variants do not influence MM risk., Instituto de Salud Carlos III (Madrid, Spain; PI17/02256 and PI20/01845), Consejería de Salud y Familia de la Junta de Andalucía (PY20/01282), Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS (01ZX1309)
Published: 2023

6. Consumption of ultra-processed foods associated with weight gain and obesity in adults: A multi-national cohort study

Author: Salvatore Panico, Vivian Viallon, José María Huerta, Heinz Freisling, Miguel Rodríguez-Barranco, Christopher Millett, Marc J. Gunter, Paolo Vineis, Christina C. Dahm, Giovanna Masala, Nasser Laouali, Elisabete Weiderpass, Verena Katzke, Charlotta Rylander, Lousie Brunkwall, Yvonne T. van der Schouw, Franziska Jannasch, Aurelio Barricarte, Fernanda Rauber, Carlos Augusto Monteiro, Jie Zhang, Jeroen W.G. Derksen, Paula Jakszyn, Geneviève Nicolas, Reynalda Cordova, Karl-Heinz Wagner, Renata Bertazzi Levy, Corinne Casagrande, Marie-Christine Boutron-Ruault, Francesca Mancini, Stina Ramne, Stina Bodén, Eszter P. Vamos, Guri Skeie, Anne Tjønneland, Jytte Halkjær, Aurora Perez-Cornago, Bernard Srour, Inge Huybrechts, Nathalie Kliemann, Sara Grioni, Matthias B. Schulze, Alicia K Heath, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Deutsches Krebsforschungszentrum, DKFZ, National Research Council, NRC, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C570/A16491, C8221/A19170, World Cancer Research Fund, WCRF, Institut National de la Santé et de la Recherche Médicale, Inserm, Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP: 2016/14302-7, Österreichischen Akademie der Wissenschaften, ÖAW, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Fondation de France: 00081166, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, School for Public Health Research, NIHR SPHR, The Public Health Policy Evaluation Unit is grateful for support from the NIHR School for Public Health Research . Swedish Cancer Society , Swedish Research Council and County Council of Västerbotten , Sweden., This work was partially financially supported by the Fondation de France (FDF, grant no. 00081166 , HF, RC)., Fernanda Rauber is a beneficiary of a postdoctoral fellowship from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) , grant numbers 2016/14302-7 ., The national cohorts are supported by the following funders: Ligue Contre le Cancer , Institut Gustave-Roussy , Mutuelle Générale de l'Education Nationale , Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid , German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health,Welfare and Sports (VWS) , Netherlands Cancer Registry (NKR) , LK Research Funds , Dutch Prevention Funds , Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS-ISCIII) , the Regional Governments of Andalucía , Asturias , Basque Country, Murcia , Navarra , and the Catalan Institute of Oncology (Barceloan), Spain), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK)., Reynalda Cordova is a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Nutritional Sciences, University of Vienna.This work was partially financially supported by the Fondation de France (FDF, grant no. 00081166, HF, RC).Fernanda Rauber is a beneficiary of a postdoctoral fellowship from the Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP), grant numbers 2016/14302-7.The national cohorts are supported by the following funders: Ligue Contre le Cancer, Institut Gustave-Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany), Dutch Ministry of Public Health,Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland),World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS-ISCIII), the Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barceloan), Spain), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).The Public Health Policy Evaluation Unit is grateful for support from the NIHR School for Public Health Research. Swedish Cancer Society, Swedish Research Council and County Council of V?sterbotten, Sweden.
Subjects: Male, NOVA, Food Handling, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Overweight, Critical Care and Intensive Care Medicine, DISEASE, Body Mass Index, 0302 clinical medicine, Risk Factors, Weight management, Prevalence, PARTICIPANTS, Poisson Distribution, Prospective Studies, 030212 general & internal medicine, 2. Zero hunger, RISK, 0303 health sciences, Nutrition and Dietetics, Middle Aged, CANCER, AGES, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Multilevel Analysis, Female, medicine.symptom, Cohort study, Adult, DIET, 03 medical and health sciences, Ultra-processed foods, medicine, Humans, Adults, Obesity, VALIDITY, Weight gain, Aged, Nutrition & Dietetics, business.industry, medicine.disease, Diet, PRODUCTS, Relative risk, Linear Models, Fast Foods, 1111 Nutrition and Dietetics, business, Body mass index, Demography
Abstract: Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity. Methods: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI). Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0.12 kg/5 years, 95% CI 0.09 to 0.15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1.11, 1.19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1.09, 1.23) of becoming obese in participants who were overweight at baseline. Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management. (c) 2021 Published by Elsevier Ltd.
Published: 2021
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7. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author: Vittorio Krogh, Rudolf Kaaks, Yvonne T. van der Schouw, Gianluca Severi, Eva Ardanaz, Marc J. Gunter, Tilman Kühn, Nicholas J. Wareham, Timothy J. Key, Francesca Mancini, Carlotta Sacerdote, María José Sánchez, Heiner Boeing, Annemieke M.W. Spijkerman, Peter M. Nilsson, Guy Fagherazzi, Miren Dorronsoro, María Dolores Chirlaque, Kay-Tee Khaw, Olov Rolandsson, Stephen J. Sharp, Salvatore Panico, Domenico Palli, Nita G. Forouhi, Christiane S. Hampe, Claudia Langenberg, Kim Overvad, Rosario Tumino, Elio Riboli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), LSHM_CT_2006_037197 N∫ 6236 National Institutes of Health, NIH: DK26190 Compagnia di San Paolo Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Medical Research Council, MRC: MC_UU_12015/1, MC_UU_12015/5, MR/N003284/1 Cancer Research UK, CRUK World Cancer Research Fund, WCRF Bundesministerium für Bildung und Forschung, BMBF Västerbotten Läns Landsting Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agentschap NL: IGE05012 Vetenskapsrådet, VR Umeå Universitet Bundesministerium für Forschung und Technologie, BMFT Deutsche Krebshilfe Bundesministerium fÃ¼r Bildung und Frauen, BMBF Stichting Diabetes Onderzoek Nederland NIHR Imperial Biomedical Research Centre, BRC NIHR Cambridge Biomedical Research Centre: IS-BRC-1215-20014, O. Rolandsson: The Västerboten County Council, M. Dorronsoro: We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment, R. Kaaks: German Cancer Aid, German Ministry of Research (BMBF), K. T. Khaw: Medical Research Council UK, Cancer Research UK, T. Kühn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), S. Panico: Compagnia di San Paolo, A. M. W. Spijkerman: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Statistics Netherlands (the Netherlands), EPIC Ragusa acknowledges for their participation blood donors of AVIS-Ragusa (local blood donors association), Y. T. van der Schouw: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Dutch ZON (Zorg Onderzoek Nederland), WCRF, Statistics Netherland, E. Riboli: Imperial College Biomedical Research Centre., Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (N∫ 6236), EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government, RK: German Cancer Aid, the German Ministry of Research (BMBF), TJK: Cancer Research UK, KTK: the Medical Research Council UK, Cancer Research UK, PMN: the Swedish Research Council, KO: the Danish Cancer Society, SP: Compagnia di San Paolo, AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds, NGF: MRC core support (MC_UU_12015/5), NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Acknowledgements, We thank all EPIC participants and staff for their contribution to this study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data and the laboratory team at the MRC Epidemiology Unit, Cambridge for managing the blood samples for the EPIC-InterAct project. We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as the team of trained nurses who participated in the recruitment. O. Rolandsson: The V?sterboten County Council, T. K?hn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), E. Riboli: Imperial College Biomedical Research Centre. Some of the data were presented as an abstract at the 54th EASD Annual Meeting in 2018., Rolandsson, Olov [0000-0002-1341-6828], and Apollo - University of Cambridge Repository
Subjects: Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Autoimmunity, Type 2 diabetes, medicine.disease_cause, LADA, Endocrinology, Autoantibody, 0302 clinical medicine, POPULATION, RISK, 0303 health sciences, Glutamate Decarboxylase, ANTIBODY POSITIVITY, GAD, Middle Aged, Phenotype, Genetic risk score, Pathophysiology, 3. Good health, Diabetes and Metabolism, Type 1 diabetes, Endokrinologi och diabetes, Female, Life Sciences & Biomedicine, Adult, 030209 endocrinology & metabolism, Endocrinology and Diabetes, Antibodies, Article, 1117 Public Health and Health Services, Endocrinology & Metabolism, 03 medical and health sciences, GLUTAMIC-ACID DECARBOXYLASE, Insulin resistance, Diabetes mellitus, Internal Medicine, medicine, Humans, TYPE-1, Aged, 030304 developmental biology, Science & Technology, business.industry, RECOGNITION, 1103 Clinical Sciences, ADULTS, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Immunology, 1114 Paediatrics and Reproductive Medicine, AUTOANTIBODIES, indident diabetes, business
Abstract: Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
Published: 2019
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8. Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium

Author: Pierre Laurent-Puig, Yan Ren, Frédérique Rachédi, Pascal Guénel, Sandya Liyanarachchi, Asta Försti, Albert de la Chapelle, Om Kulkarni, Claire Mulot, Huiling He, Federica Gemignani, Julie Guibon, Anne-Valérie Guizard, Fabienne Lesueur, Rossella Elisei, Ausrele Kesminiene, Anthony F. Herzig, Mojgan Karimi, Pierre-Emmanuel Sugier, Thérèse Truong, Delphine Bacq-Daian, Anne-Louise Leutenegger, Constance Xhaard, Daniel F. Comiskey, Celia M Pereda, Evgenia Ostroumova, Florent de Vathaire, Elisabeth Adjadj, Françoise Borson-Chazot, Jean-François Deleuze, Carole Rubino, Anne Boland-Auge, Hauke Thomsen, Elise A. Lucotte, Marie-Christine Boutron-Ruault, Juan J Lence-Anta, Rosa Ortiz, Claire Schvartz, Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris-Saclay, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Épidémiologie des radiations, épidémiologie clinique des cancers et survie (U1018 (Équipe 3) ), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Institut Jean Godinot [Reims], UNICANCER, Registre Général des Tumeurs du Calvados, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Taaone, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institute of Oncology and Radiobiology, Ohio State University [Columbus] (OSU), University of Pisa - Università di Pisa, Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], German Cancer Consortium [Heidelberg] (DKTK), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, MESRI: 2102 918823 National Institute of Ecology, NIE Agence Nationale de la Recherche, ANR: ANR‐10‐COHO‐0006 Fondation ARC pour la Recherche sur le Cancer, ARC: PGA120150202302 Ligue Contre le Cancer Fondation de France Institut National Du Cancer, INCa: 9533 Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES Mutuelle Générale de l'Education Nationale, MGEN Electricité de France, EDF: EP 2019‐01, We thank Dr Yannick Rougier and Dr Dominique Baron-Dubourdieu for providing pathological reports for the NC study, as well as Dr Sylvie Laumond, Dr Jean-Paul Grangeon (Direction des affaires sanitaires et sociales de Nouvelle-Cal?donie) and the country's provincial health authorities (DPASS Sud, DPASS Nord, DPASS Iles Loyaut?) for support during data collection in the NC study. We thank Milagros Velasco, Mae Chappe and Idalmis Infante (Institute of Oncology and Radiobiology, La Havana, Cuba) and Silvia Turcios (National Institute of Endocrinology, La Havana, Cuba) for helping in the collection of the data in the Cuban Study. We thank John Paoaafaite and Joseph Teuri who contacted and interviewed cases and controls for the study. Finally, we also thank P. Morales, J. Iltis, P. Giraud, P. Didiergeorge, M. Brisard, G. Soubiran, B. Caillou, P. Dupire, J. Ienfa, G. de Clermont, N. Cerf, B. Oddo, M. Bambridge, C. Baron, A. Mouchard-Rachet, O. Simonet, D. Lamarque, J. Vabret, J. Delacre, M.P. Darquier and J. Leninger, for their help in the collection of the cases or in the organization of study in French Polynesia. We would like to thank the Association Centre de Regroupement Informatique et Statistique en Anatomie Pathologique en Provence-Alpes-C?te d'Azur (CRISAP PACA), as well as Dr Arlette Danzon, Dr Genevi?ve Sasolas, Dr Marc Christophe Sattonnet, Dr Marc Colonna, Dr Brigitte Lacour, Dr Michel Velten, Dr Enora Clero, Dr St?phane Maillard, Dr Laurent Bailly, Dr Eug?nia Marin? Barjoan, Dr Jean-Luc Lassalle, Dr Z Hafdi-Nejjari, Dr P Delafosse, Dr Elisabeth Adjadj, Kami-Marie Moreau, Cyrielle Orenes, Laurianne Sarrazin, St?phanie Bonnay, Fr?d?rique Chatelain, Maryse Barouh, Evelyne Rapp, Julie Festra?ts, Julie Valbousquet, Yusuf Atilgan, Jean Chappellet, Lallia Bedhouche, Florent Dayet and Ziyan Fami, for their help in the collection of cases, the organization and the management of the Young-Thyr study. We acknowledge Stefano Landi for the Italian GWAS data and Subhayan Chattopadhyay and Yasmeen Niazi (Division of Molecular Genetic Epidemiology, German Cancer Research Center?DKFZ) for technical assistance in these data analysis. We are grateful to Dr Herv? Perdry for his help in using the GASTON package. The EPITHYR GWAS was supported by Institut National du Cancer (grant number 9533) and Fondation ARC (grant number PGA120150202302). The E3N cohort received support from the MGEN, Gustave Roussy and Ligue contre le cancer for its setup and maintenance. The E3N cohort was also supported by a state grant from the Agence Nationale pour la Recherche (ANR) (grant number ANR-10-COHO-0006) within the Investissement d'Avenir program and from the French Ministry of Higher Education, Research and Innovation (MESRI, grant number 2102 918823). The other participating studies were funded by Ligue Nationale Contre le Cancer, ANR, the Direction G?n?rale de la Sante, the Agence Fran?aise de S?curit? Sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHILDTHYR EEC program, and the Fondation de France. JG was the recipient of a PhD fellowship from R?gion Ile-de-France, part of OK was the recipient of a post-doc fellowship from Electricit? de France (conseil scientifique de Radioprotection d'EDF, grant EP 2019-01)., The EPITHYR GWAS was supported by Institut National du Cancer (grant number 9533) and Fondation ARC (grant number PGA120150202302). The E3N cohort received support from the MGEN, Gustave Roussy and Ligue contre le cancer for its setup and maintenance. The E3N cohort was also supported by a state grant from the Agence Nationale pour la Recherche (ANR) (grant number ANR‐10‐COHO‐0006) within the Investissement d'Avenir program and from the French Ministry of Higher Education, Research and Innovation (MESRI, grant number 2102 918823). The other participating studies were funded by Ligue Nationale Contre le Cancer, the Direction Générale de la Sante, the Agence Française de Sécurité Sanitaire de l'alimentation, and the Fondation de France. JG was the recipient of a PhD fellowship from Région Ile‐de‐France, part of OK was the recipient of a post‐doc fellowship from Electricité de France (conseil scientifique de Radioprotection d'EDF, grant EP 2019‐01)., Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Male, Cancer Research, Native Hawaiian or Other Pacific Islander, [SDV]Life Sciences [q-bio], Ethnic group, Genome-wide association study, 0302 clinical medicine, Gene Frequency, Informed consent, Epidemiology, thyroid cancer, Chromosomes, Human, Medicine, Prospective cohort study, Thyroid cancer, Genetics, 0303 health sciences, education.field_of_study, Incidence (epidemiology), Middle Aged, Checklist, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Pacific islanders, Female, Adult, medicine.medical_specialty, case-control study, education, Population, Biology, Pacific Islands, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Humans, Genetic Predisposition to Disease, Thyroid Neoplasms, Aged, 030304 developmental biology, genome-wide association study, business.industry, Case-control study, medicine.disease, Clinical trial, Case-Control Studies, Family medicine, business
Abstract: Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. Here, we conducted a genome-wide association study (GWAS) involving 1,554 cases/1,973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from the EPITHYR consortium. Our results confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 (rs334729) and 16q23.2 (rs16950982), which were associated with TSH levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. The frequency of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans and may explain part of the highest DTC incidence observed in Oceanians.Competing Interest StatementThe authors have declared no competing interest.Funding StatementINCA (grant number 9533) and ARC (grant number PGA120150202302), Ligue Nationale Contre le Cancer, Agence Nationale pour la Recherche (ANR), the Direction Generale de la Sante, the Agence Francaise de Securite Sanitaire de l alimentation, de lenvironnement et du travail (ANSES), CHILDTHYR EEC program, and the Fondation de France. JG and CX were the recipient of a PhD fellowship from Region Ile-de-France.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All participants provided informed consent and each study was approved by their governing ethics committee.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. (Less)
Published: 2021
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9. A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Author: Ingegerd Johansson, David S. Lopez, Alicia K Heath, Amanda J. Cross, Anne Tjønneland, J. Ramón Quirós, Melissa A. Merritt, Paula Jakszyn, Bas Bueno-de-Mesquita, Pilar Amiano, Anne Kirstine Eriksen, Manuela M. Bergmann, Marc J. Gunter, Bernard Srour, David C. Muller, Piet A. van den Brandt, Matthias B. Schulze, Salvatore Panico, Claudia Agnoli, Pietro Ferrari, Marco Lukic, José María Huerta, Christina C. Dahm, Therese Haugdahl Nøst, Areti Papadopoulou, Aurelio Barricarte Gurrea, Rosario Tumino, María José Sánchez, Fulvio Ricceri, Nadia Bastide, Paolo Vineis, Ulrika Ericson, Eva Ardanaz, Gianluca Severi, Guri Skeie, Aurora Perez-Cornago, Nikos Papadimitriou, Emmanouil Bouras, Elisabete Weiderpass, Ellio Riboli, Ioanna Tzoulaki, Heiner Boeing, Stina Bodén, Giovanna Masala, Jeroen W.G. Derksen, Jonna Berntsson, Verena Katzke, Elena Critselis, Konstantinos K. Tsilidis, University of Ioannina, Maastricht University [Maastricht], Imperial College London, Biomedical Research Foundation of the Academy of Athens (BRFAA), International Agency for Cancer Research (IACR), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Hawai'i [Honolulu] (UH), The University of Texas Health Science Center at Houston (UTHealth), University of Oxford [Oxford], University of Potsdam, The Arctic University of Norway (UiT), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Umeå University, Università degli studi di Torino = University of Turin (UNITO), Lund University [Lund], Instituto de Salud Carlos III [Madrid] (ISC), Aarhus University [Aarhus], IRCCS Istituto Nazionale dei Tumori [Milano], University of Copenhagen = Københavns Universitet (KU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Naples Federico II, La Salle [Ramon Llull University], Utrecht University [Utrecht], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, International Council of Ophthalmology, ICO, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF: WCRF 2014/1180, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme (WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (ICO) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme ( WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre . The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research ( BMBF ) (Germany), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)– Instituto de Salud Carlos III ( ISCIII ), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ( ICO ) (Spain), Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Epidemiologie, and RS: GROW - R1 - Prevention
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Riboflavin, colorectal cancer, Lower risk, Cohort Studies, Animal science, beta-Carotene, Risk Factors, Epidemiology, medicine, cohort study, Humans, Prospective Studies, Hepatology, Gastroenterology & Hepatology, business.industry, Hazard ratio, Gastroenterology, food and beverages, 1103 Clinical Sciences, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Diet, epidemiology, nutrition, business, Colorectal Neoplasms, Cohort study
Abstract: Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93–0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.
Published: 2020
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10. Association between anthropometry and lifestyle factors and risk of B cell lymphoma: an exposome wide analysis

Author: Anne Tjønneland, Claudia Agnoli, Pietro Ferrari, Pilar Amiano, Bas Bueno-de-Mesquita, Miguel Rodríguez-Barranco, Alexandra Nieters, Aurelio Barricarte, Roel Vermeulen, Elisabete Weiderpass, Giovanna Masala, José María Huerta, Marta Solans, Delphine Casabonne, Federico Canzian, Caroline Besson, Florentin Späth, Gianluca Severi, Carlotta Sacerdote, James McKay, Catalina Bonet, Sabine Naudin, Fatemeh Saberi Hosnijeh, Sofia Christakoudi, Heinz Freisling, Rosario Tumino, Kristin Benjaminsen Borch, Rudolf Kaaks, Matthias B. Schulze, Yolanda Benavente, Anja Olsen, Charlotta Rylander, Anika Knuppel, Marie Christine Boutron Ruault, Mats Jerkeman, Immunology, Centre international de Recherche sur le Cancer (CIRC), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 179 2017SGR1085 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: 205212/Z/16/Z National Research Council, NRC Medical Research Council, MRC: MR/M012190/1 Cancer Research UK, CRUK: 14136, C570/A11692, C570/A16491 World Cancer Research Fund, WCRF European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF: 01EO1303 Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR Ligue Contre le Cancer Vetenskapsrådet, VR NordForsk Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN European Regional Development Fund, ERDF: ERC2009‐AdG 232997, PI13/00061, PI13/01162, PI14/01219, PI17/01280 Hellenic Health Foundation, HHF, Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), CERCA Programme/Generalitat de Catalunya for institutional support, Grant/Award Number: 2017SGR1085, Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Cancer Research UK, Grant/Award Numbers: 14136 (to EPIC‐Norfolk), C570/A11692, C570/A16491, Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), (Spain), Danish Cancer Society (Denmark), TRANSCAN/Dutch Cancer Society, Grant/Award Number: 179, NOVEL consortium, Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), European Commission (DG‐SANCO), Federal Ministry of Education and Research (BMBF), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research, Grant/Award Number: BMBF 01EO1303, German Institute of Human Nutrition Potsdam‐Rehbruecke, Nuthetal (Germany), Institut Gustave Roussy, Institut National de la Sante et de la Recherche Medicale (France), International Agency for Research on Cancer, Ligue Natinale Contre le Cancer, LK Research Funds, Medical Research Council, Grant/Award Numbers: 1000143 (to EPIC‐Norfolk), MR/M012190/1 (to EPIC‐Oxford), Mutuelle Generale de l'Education Nationale, Netherlands Cancer Registry (NKR), Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Spanish Ministry of Economy and Competitiveness ‐ Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) ‐ a way to build Europe, Grant/Award Numbers: PI13/00061 (to Granada), PI13/01162 (to EPIC‐Murcia), PI17/01280, PI14/01219 (to Barcelona), Statistics Netherlands (The Netherlands), Grant/Award Number: Grant number: ERC2009‐AdG 232997, Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Vasterbotten (Sweden), the Hellenic Health Foundation (Greece), Wellcome Trust, Grant/Award Number: 205212/Z/16/Z, and World Cancer Research Fund (WCRF) Funding information
Subjects: Oncology, Male, Limfomes, Cancer Research, Lymphoma, Follicular lymphoma, Cohort Studies, 0302 clinical medicine, Risk Factors, Prospective Studies, Càncer, Prospective cohort study, B-cell lymphoma, Cancer, 2. Zero hunger, wide association study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Anthropometry, exposome wide association study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Plasma cell neoplasm, Middle Aged, exposome‐, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, exposome&#8208, MEDITERRANEAN DIET, 030220 oncology & carcinogenesis, OBESITY, Lymphomas, Female, SMOKING, NON-HODGKIN-LYMPHOMA, Life Sciences & Biomedicine, Cancer Epidemiology, prospective study, NATIONAL-HEALTH, medicine.medical_specialty, Inverse Association, lifestyle, Lymphoma, B-Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphoma, exposome‐wide association study, exposome, DIETARY-FAT, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, VALIDITY, Life Style, Cancer och onkologi, Science & Technology, Proportional hazards model, business.industry, medicine.disease, exposome-wide association study, PHYSICAL-ACTIVITY, PROSPECTIVE COHORT, Cancer and Oncology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: To better understand the role of individual and lifestyle factors in human disease, an exposome‐wide association study was performed to investigate within a single‐study anthropometry measures and lifestyle factors previously associated with B‐cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed‐up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B‐cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL., What's new? The “exposome” includes all non‐genetic exposures (e.g. diet, viral, environmental, etc.), with the goal of understanding how those exposures may affect an individual's health. In this study, the authors used a technique called “EWAS” (exposome‐wide association study) to identify multiple factors that are associated with B‐cell lymphoma (BCL) risk. Their results confirm both previously reported risk factors and protective factors. In addition, they identify several previously unknown associations. These new insights, gained via the analysis of multiple exposures, suggest that traditional single‐factor approaches may be suboptimal compared with an EWAS approach.
Published: 2020
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11. Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

Author: Fulvio Ricceri, Tilman Kühn, Marc J. Gunter, Guri Skeie, Roel Vermeulen, Sabina Sieri, Elio Riboli, Aurora Perez-Cornago, Heather Ward, Amanda J. Cross, Verena Katzke, José María Huerta, Manuela M. Bergmann, Konstantinos K. Tsilidis, Yahya Mahamat-Saleh, Eva Ardanaz, Antonia Trichopoulou, Salvatore Panico, Elisabete Weiderpass, Cecilie Kyrø, Rosario Tumino, Antonio Agudo, María José Sánchez, Alexandra Vulcan, Valerie Cayssials, Giovanna Masala, Pilar Amiano, Dorthe Nyvang, Genevieve Buckland, Paula Jakszyn, Eleni Peppa, Mazda Jenab, Bodil Ohlsson, Marie-Christine Boutron-Ruault, Anne Tjønneland, Anna Karakatsani, Heiner Boeing, Franck Carbonnel, Christina C. Dahm, Cristina Lasheras, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, 14136 VetenskapsrÃ¥det, VR Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium fÃ¼r Bildung und Forschung, BMBF Bundesministerium fÃ¼r Bildung und Frauen, BMBF Institut National de la SantÃ© et de la Recherche MÃ©dicale, Inserm KrÃ¦ftens BekÃ¦mpelse, DCS Instituto de Salud Carlos III, ISCIII: PI15/00639 German Cancer Research Center, DKFZ National Research Council, NRC 6236 Generalitat de Catalunya European Commission, EC European Regional Development Fund, FEDER Centre International de Recherche sur le Cancer, CIRC RD06/0020 Deutsche Krebshilfe German Cancer Research Center, DKFZ PI13/01162, PI13/00061 Cancerfonden World Cancer Research Fund, WCRF: ERC-2009-AdG 232997 NordForsk Associazione Italiana per la Ricerca sul Cancro, AIRC Medical Research Council, MRC: MR/M012190/1 European Regional Development Fund, FEDER, Our study has been funded by Instituto de Salud Carlos III through the project PI15/00639 (Co-funded by European Regional Development Fund [ERDF], a way to build Europe). We thank CERCA Programme/Generalitat de Catalunya for institutional support. Regional Government of Asturias, German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM, France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020, Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPICNorfolk, and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPICNorfolk, MR/M012190/1 to EPIC-Oxford, United Kingdom).
Subjects: Oncology, Male, Cancer Research, Colorectal cancer, Cohort Studies, 0302 clinical medicine, MARKERS, Risk Factors, ATHEROSCLEROSIS MAASTRICHT CODAM, Prospective Studies, LOW-GRADE INFLAMMATION, Prospective cohort study, INDEX, Abdominal obesity, biology, Hazard ratio, GLUCOSE-METABOLISM, Middle Aged, C-REACTIVE PROTEIN, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, inflammatory potential of the diet, 030220 oncology & carcinogenesis, Cohort, Adenocarcinoma, Regression Analysis, Female, epidemiology, medicine.symptom, Colorectal Neoplasms, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, prospective cohort, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, MECHANISMS, Association, 03 medical and health sciences, COLON, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Obesity, Exercise, Inflammation, Science & Technology, business.industry, association, C-reactive protein, Feeding Behavior, medicine.disease, digestive system diseases, Diet, PHYSICAL-ACTIVITY, Nutrition Assessment, Multivariate Analysis, biology.protein, business
Abstract: Pro-inflammatory diets are associated with risk of developing colorectal cancer (CRC), however inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute towards a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumours). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More pro- inflammatory diets were related to a higher CRC risk, particularly for colon cancer; Hazar Ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval (CI) 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS were 1.62 (95% CI 1.31- 2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. This study shows that more pro-inflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men. This article is protected by copyright. All rights reserved.
Published: 2020
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12. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

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

Author: Patrick Arveux, Elio Riboli, Carla H. van Gils, Marina Kvaskoff, Rudolf Kaaks, María José Sánchez, Kim Overvad, Pilar Amiano, Naomi E. Allen, Elisabete Weiderpass, Christina C. Dahm, Catalina Bonet, Carlo La Vecchia, Giovanna Masala, Amalia Mattiello, José Ramón Quirós, Manuela M. Bergmann, Matthias B. Schulze, Marc J. Gunter, Anna Karakatsani, Daniel Ángel Rodríguez-Palacios, Vivian Viallon, Valeria Pala, Ruth C. Travis, Renée T. Fortner, Fulvio Ricceri, Rosario Tumino, Antonia Trichopoulou, Evelyn M. Monninkhof, Anne Tjønneland, Laure Dossus, Agnès Fournier, Aurelio Barricarte Gurrea, Anika Hüsing, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cancer Research Foundation in Northern Sweden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, C570/A16491 Vetenskapsrådet, VR Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Associazione Italiana per la Ricerca sul Cancro, AIRC National Research Council, NRC Mutuelle Générale de l'Education Nationale, MGEN Hellenic Health Foundation, HHF Institut National de la Santé et de la Recherche Médicale, Inserm Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, IARC RD06/0020 German Cancer Research Center, DKFZ Deutsche Krebshilfe Cancerfonden World Cancer Research Fund, WCRF: ERC‐2009‐AdG 232997 PI13/01162, PI13/00061 NordForsk Medical Research Council, MRC: MR/M012190/1, The coordination of EPIC is financially supported by the European Commission (DG‐SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC‐2009‐AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC‐Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten, The Cancer Research Foundation of Northern Sweden (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170), Medical Research Council (MR/M012190/1) (EPIC‐Oxford, and United Kingdom). The EPIC‐Norfolk study (doi: 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php .
Subjects: Cancer Research, primary prevention, Overweight, Body Mass Index, COLORECTAL-CANCER, Cohort Studies, 0302 clinical medicine, Endometrial cancer, Medicine, risk factors, endometrial cancer, 2. Zero hunger, Framingham Risk Score, Incidence, Incidence (epidemiology), Middle Aged, 3. Good health, Europe, Menopause, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, NUTRITION, medicine.symptom, Cancer Epidemiology, Adult, Pes corporal, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), BREAST, OVARIAN-CANCER, 03 medical and health sciences, Humans, Risk factor, Hormone therapy, Aged, Models, Statistical, business.industry, ORAL-CONTRACEPTIVE USE, Body weight, medicine.disease, Endometrial Neoplasms, Càncer d'endometri, business, Body mass index, Hormonoteràpia, Contraceptives, Oral, Demography
Abstract: Endometrial cancer (EC) incidence rates vary ~10‐fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low‐risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow‐up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2) and HT use (to all non‐HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks., What's new? Endometrial cancer rates vary considerably around the world, with incidence rates higher in Europe and North America than in parts of Asia and Africa. Here, the authors investigated how much of the risk disparity arises from modifiable factors, and how much modifying these factors could reduce cancer incidence. The 10% of European women with lowest risk had similar incidence to women in low‐risk countries, they found. Their model predicted that in European women, maintaining BMI below 23 kg/m2 and avoiding postmenopausal hormone use could reduce risk by 30%. Long‐term use of oral contraceptives could reduce risk by 42.5%.
Published: 2020
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14. Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

Author: Magritt Brustad, Veronika Fedirko, Marc J. Gunter, Anja Olsen, Antonia Trichopoulou, Geneviève Nicolas, Anna Karakatsani, Veronique Chajes, Gianluca Severi, Elom K. Aglago, Eva Ardanaz, Aurora Perez-Cornago, Kim Overvad, Cristina Lasheras, Salvatore Panico, Verena Katzke, Bas Bueno-de-Mesquita, José María Huerta, Neil Murphy, Christina C. Dahm, Maria Wennberg, Teresa Norat, Bodil Ohlsson, Elisabete Weiderpass, Antonio Agudo, Heather Ward, Anne Tjønneland, Valeria Pala, Tilman Kühn, Bethany Van Guelpen, Guri Skeie, Rosario Tumino, María José Sánchez, A. M. May, Corinne Casagrande, Jeroen W.G. Derksen, Marie-Christine Boutron-Ruault, Elio Riboli, Agnès Fournier, Sophie Hellstrand, Inge Huybrechts, Georgia Martimianaki, Alessio Naccarati, Tobias Pischon, Amanda J. Cross, Pilar Amiano, Domenico Palli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), RD06/0020 6236 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: C570/A16491, C8221/A19170, MR/M012190/1 National Research Council, NRC Medical Research Council, MRC British Heart Foundation, BHF Cancer Research UK, CRUK World Cancer Research Fund, WCRF: WCRF 2013/1002 Food Standards Agency, FSA Stroke Association European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Associazione Iblea per la Ricerca Epidemiologica, AIRE Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Fondation Gustave Roussy Hellenic Health Foundation, HHF, Funding Supported by a grant from the World Cancer Research Fund ( WCRF ) to Marc Gunter (grant number: WCRF 2013/1002 ). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer . The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l'Education Nationale , and Institut National de la Santé et de la Recherche Médicale ( INSERM ) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), and Federal Ministry of Education and Research ( BMBF ) (Germany), Hellenic Health Foundation , Stavros Niarchos Foundation , and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer ( AIRC ), National Research Council , and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu ( AVIS ) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry ( NKR ), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), and Statistics Netherlands (the Netherlands), Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucía , Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II ( ISCIII RETIC) ( RD06/0020 ) (Spain), Swedish Cancer Society , Swedish Scientific Council , and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK , Medical Research Council , Stroke Association , British Heart Foundation , Department of Health , Food Standards Agency , the Wellcome Trust (UK), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Funding Supported by a grant from the World Cancer Research Fund (WCRF) to Marc Gunter (grant number: WCRF 2013/1002). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigaci?n Biom?dica en Red en Epidemiolog?a y Salud P?blica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Colorectal cancer, [SDV]Life Sciences [q-bio], Àcids grassos insaturats, Physiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Càncer colorectal, Fatty Acids, Omega-3, Medicine, Animals, Humans, Prospective Studies, 2. Zero hunger, chemistry.chemical_classification, Unsaturated fatty acids, Epidemiologic, Gastroenterology & Hepatology, Hepatology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, Gastroenterology, Fishes, 1103 Clinical Sciences, Odds ratio, medicine.disease, Eicosapentaenoic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Diet, chemistry, Seafood, Docosahexaenoic acid, 030220 oncology & carcinogenesis, Omega 3, Cohort, Colonic Neoplasms, Tumorigenesis, 030211 gastroenterology & hepatology, Docosapentaenoic acid, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Polyunsaturated fatty acid
Abstract: Background & Aims There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
Published: 2020
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15. Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort

Author: Agnès Fournier, Eva Lundin, N. Charlotte Onland-Moret, Louise Hansen, Elisavet Valanou, Marina Kvaskoff, Leire Gil, Inger T. Gram, Rosario Tumino, Marc J. Gunter, Annika Idahl, Rudolf Kaaks, Noemi Bender, Eric J. Duell, María José Sánchez, Carlotta Sacerdote, Kristian Riesbeck, Sandra González Maldonado, Claudia Agnoli, Anne Tjønneland, Charlotte Le Cornet, Renée T. Fortner, Laure Dossus, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Antonia Trichopoulou, Amalia Mattiello, José Ramón Quirós, Aurelio Barricarte, Maria Dolores Chirlaque, Tim Waterboer, Eleni Peppa, Domenico Palli, Jenny Brändstedt, Kay-Tee Khaw, Aurora Perez-Cornago, Heiner Boeing, Umeå University, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Danish Cancer Society Research Center, Copenhagen, Denmark, parent, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Hellenic Health Foundation, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, I-20133 Milano, Italy, University of Naples Federico II, Civile - M.P.Arezzo Hospital, Center for Cancer Prevention (CPO-Piemonte), Universiteit Utrecht, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France. Electronic address: steliarova@iarc.fr., Catalan Institute of Oncology (ICO-IDIBELL), Hospitales Universitarios de Granada/Universidad de Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIB-Arrixaca [Murcia, Spain], Universidad de Murcia, Public Health Institute of Navarra, Pamplona, Spain, and CIBER Epidemiología y Salud Pública (CIBERESP), IdiSNA, Navarra Institute for Health Research, Public Health Division of Gipuzkoa, Institute BIO Donostia-Health Department, Skane University Hospital [Lund], Department of Translational Medicine [Malmö, Sweden] (Clinical Microbiology), Lund University [Lund, Sweden], University of Cambridge [UK] (CAM), University of Oxford [Oxford], Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, C570/A16491 VetenskapsrÃ¥det, VR Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Bundesministerium fÃ¼r Bildung und Forschung, BMBF Bundesministerium fÃ¼r Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm KrÃ¦ftens BekÃ¦mpelse, DCS CAN 2016/545 German Cancer Research Center, DKFZ National Research Council, NRC Cancer Research Foundation in Northern Sweden European Commission, EC Centre International de Recherche sur le Cancer, IARC RD06/0020 German Cancer Research Center, DKFZ Cancerfonden PI13/01162, PI13/00061 World Cancer Research Fund, WCRF: ERC-2009-AdG 232997 NordForsk Associazione Italiana per la Ricerca sul Cancro, AIRC Medical Research Council, MRC: MR/M012190/1, This work was supported by grants from The Cancer Research Foundation in Northern Sweden and The County Council of V?sterbotten, Sweden, and the German Cancer Research Center. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Additional funding received from the Anna and Edwin Berger Foundation (K.R.), Malm? Hospital Cancer Foundation (K.R.), Cancerfonden (CAN 2016/545 to K.R.).
Subjects: Oncology, Cancer Research, endocrine system diseases, Càncer d'ovari, Chlamydia trachomatis, Mycoplasma genitalium, Carcinoma, Ovarian Epithelial, medicine.disease_cause, Serology, 0302 clinical medicine, Risk Factors, Pelvic inflammatory disease, Prospective Studies, human papillomavirus, Aged, 80 and over, Ovarian Neoplasms, Sexually transmitted diseases, Human papillomavirus 16, Chlamydia, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, biology, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Serous fluid, ovarian cancer, 030220 oncology & carcinogenesis, Female, Malalties de transmissió sexual, Adult, Risk, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Ovarian cancer, Internal medicine, medicine, Humans, Neoplastic transformation, Aged, business.industry, Papillomavirus Infections, Chlamydia Infections, biology.organism_classification, medicine.disease, herpes simplex virus, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Relative risk, Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Biomarkers
Abstract: International audience; A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.
Published: 2020
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16. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: A multinational cohort study

Author: Manuela M. Bergmann, Elio Riboli, Christina C. Dahm, Marc J. Gunter, Christina Bamia, David C. Muller, Pauline Bazelle, Antonio Agudo, Isabelle Romieu, Heather Ward, Pietro Ferrari, Patrick Arveux, Anja Olsen, Tammy Y.N. Tong, Elin Thysell, Julie A. Schmidt, María José Sánchez, Adam S. Butterworth, Aurelio Barricarte Gurrea, Peter Nilsson, Pilar Amiano, Kim Overvad, Fulvio Ricceri, Rosario Tumino, Salvatore Panico, Michael J. Sweeting, Evelyn M. Monninkhof, Anne Tjønneland, Marina Kvaskoff, Vincenzo Bagnardi, Olov Rolandsson, Konstantinos K. Tsilidis, Mazda Jenab, H. Susan J. Picavet, Paolo Vineis, Tilman Kühn, Heinz Freisling, Gianluca Severi, John Danesh, Claudia Agnoli, Hannah Lennon, Marije F. Bakker, Vivian Viallon, Virginia Menéndez, Rudolf Kaaks, Nicholas J. Wareham, Heiner Boeing, Carmen Santiuste, Jonas Manjer, Elisabete Weiderpass, Domenico Palli, Ioanna Tzoulaki, Cristian Ricci, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 2018-1-PL SHS-06-CIRC-1 LSHM_CT_2006_037197 HEALTH24 F2-2012-279233 PI13/00061, PI13/01162 2018-123 RD06/0020 G0800270, MR/ L003120/1 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, IARC National Research Council, NRC Medical Research Council, MRC: MR/M012190/1 British Heart Foundation, BHF: 26 RG/08/014, RG13/ 13/30194, SP/09/002 Cancer Research UK, CRUK: C570/A16491, C8221/A19170 World Cancer Research Fund, WCRF European Commission, EC European Research Council, ERC: 268834 Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Vetenskapsrådet, VR Ministère des Affaires Sociales et de la Santé: GR-IARC-2003-09-12-01 Direction Générale de la Compétitivité, de l’Industrie et des Services, DGCIS Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe, This work was supported by the Direction Générale de la Santé (French Ministry of Health) (Grant GR-IARC-2003-09-12-01) and by the French National Cancer Institute (INCA_N°2018-123), and the Cancéropôle Ile-de-France (N°2018-1-PL SHS-06-CIRC-1). Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). EPIC-CVD has been supported by the European Union Framework 7 (HEALTH24 F2-2012-279233), the European Research Council (268834), the UK Medical Research 25 Council (G0800270 and MR/ L003120/1), the British Heart Foundation (SP/09/002 and 26 RG/08/014 and RG13/ 13/30194), and the UK National Institute of Health Research. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report., Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Cancer Research UK, Freisling, H, Viallon, V, Lennon, H, Bagnardi, V, Ricci, C, Butterworth, A, Sweeting, M, Muller, D, Romieu, I, Bazelle, P, Kvaskoff, M, Arveux, P, Severi, G, Bamia, C, Kuhn, T, Kaaks, R, Bergmann, M, Boeing, H, Tjonneland, A, Olsen, A, Overvad, K, Dahm, C, Menendez, V, Agudo, A, Sanchez, M, Amiano, P, Santiuste, C, Gurrea, A, Tong, T, Schmidt, J, Tzoulaki, I, Tsilidis, K, Ward, H, Palli, D, Agnoli, C, Tumino, R, Ricceri, F, Panico, S, Picavet, H, Bakker, M, Monninkhof, E, Nilsson, P, Manjer, J, Rolandsson, O, Thysell, E, Weiderpass, E, Jenab, M, Riboli, E, Vineis, P, Danesh, J, Wareham, N, Gunter, M, Ferrari, P, 29790514 - Ricci, Cristian, Overvad, Kim [0000-0001-6429-7921], Dahm, Christina C [0000-0003-0481-2893], and Tong, Tammy Y N [0000-0002-0284-8959]
Subjects: Male, lcsh:Medicine, Disease, Diabete, Body Mass Index, Cohort Studies, 0302 clinical medicine, Risk Factors, Neoplasms, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Càncer, 11 Medical and Health Sciences, Cancer, 2. Zero hunger, Medicine(all), Incidence, Hazard ratio, Diabetes, General Medicine, Middle Aged, Cardiovascular disease, 3. Good health, Cardiovascular diseases, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Obesitat, Female, Type 2, Cohort study, Research Article, Adult, Alcohol Drinking, Cancer and cardiometabolic multimorbidity, Healthy lifestyle, Obesity, Prevention, Diabetes Mellitus, Type 2, Humans, Proportional Hazards Models, Risk Reduction Behavior, Life Style, Multimorbidity, 03 medical and health sciences, Environmental health, General & Internal Medicine, medicine, Journal Article, Diabetes Mellitus, Cancer och onkologi, business.industry, Proportional hazards model, Malalties cardiovasculars, lcsh:R, medicine.disease, Cancer and Oncology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index
Abstract: Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
Published: 2020
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17. Diffuse Glioneuronal tumour with Oligodendroglioma‐like features and Nuclear Clusters (DGONC) – a molecularly‐defined glioneuronal CNS tumour class displaying recurrent monosomy 14

Author: Martin U. Schuhmann, Till Milde, A. von Deimling, Matija Snuderl, Kathy Keyvani, Nada Jabado, Thorsten Pietsch, Eleonora Aronica, Olaf Witt, Christian Hartmann, David T.W. Jones, David Ellison, Felix Sahm, Martin Sill, Dominik Sturm, M Kool, M. Y. Deng, Damian Stichel, Matthias Preusser, Felice Giangaspero, K. von Hoff, M. Lauten, Christine Haberler, Ori Staszewski, Ulrich Schüller, Jonas Ecker, Pieter Wesseling, Christopher Dunham, Martin Ebinger, Jens Schittenhelm, Christel Herold-Mende, Hendrik Witt, Wolfgang Wick, Andrey Korshunov, Nicholas G. Gottardo, Dominique Figarella-Branger, Andrea Wittmann, M. Deckert, Stefan M. Pfister, Heidelberg University Hospital [Heidelberg], Tübingen University Hospital [Germany], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d’Anatomie Pathologique et de Neuropathologie, APHM, Hôpital de la Timone, Hôpital de la Timone [CHU - APHM] (TIMONE), Genome Analysis, Department of Pediatrics and Adolescent Medicine, University Freiburg, Freiburg, Institut d'écologie et des sciences de l'environnement de Paris (IEES), Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Massachusetts General Hospital [Boston], Department of Human Genetics , Department of Experimental Medicine, Radboud University Medical Center [Nijmegen], VU University Medical Center [Amsterdam], RMIT Melbourne, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Department of Neuropathology, Institute of Pathology, Division of Paediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany, Institut d'écologie et des sciences de l'environnement de Paris (iEES), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Pathology, CCA - Cancer biology, Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA), ANS - Cellular & Molecular Mechanisms, APH - Aging & Later Life, and APH - Mental Health
Subjects: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Histology, [SDV]Life Sciences [q-bio], Oligodendroglioma, Medizin, Biology, Pathology and Forensic Medicine, Central Nervous System Neoplasms, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Monosomy, Physiology (medical), medicine, Humans, Neurocytoma, ComputingMilieux_MISCELLANEOUS, Paediatric patients, Chromosomes, Human, Pair 14, Glioma, DNA Methylation, medicine.disease, 3. Good health, 030104 developmental biology, Neurology, chemistry, Homogeneous, DNA methylation, Female, Neurology (clinical), Who classification, Monosomy 14, 030217 neurology & neurosurgery, DNA, Clear cell
Abstract: Aims: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. Patients and methods: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the ‘conumee’ package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. Results: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. Conclusions: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.
Published: 2019
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18. Prospective analysis of circulating metabolites and breast cancer in EPIC

Author: José María Huerta, Salvatore Panico, Antonia Trichopoulou, Joseph A. Rothwell, Sabina Sieri, Anja Olsen, Christina C. Dahm, Ruth C. Travis, Audrey Gicquiau, Pilar Amiano, Elisabete Weiderpass, N. Charlotte Onland-Moret, Antonio Agudo, Anna Karakatsani, Isabelle Romieu, Paolo Vineis, Mathilde His, Elio Riboli, Marc J. Gunter, Guri Skeie, Tilman Kühn, Augustin Scalbert, Carla H. van Gils, Georgia Martimianaki, Therese Haugdahl Nøst, Anne Tjønneland, Heiner Boeing, Laure Dossus, Pietro Ferrari, Julie A. Schmidt, Rosario Tumino, Konstantinos K. Tsilidis, David Achaintre, Torkjel M. Sandanger, Agnès Fournier, Sofia Christakoudi, María José Sánchez, Vivian Viallon, Renée T. Fortner, Kim Overvad, Giovanna Masala, Sabina Rinaldi, J. Ramón Quirós, Gianluca Severi, Eva Ardanaz, [His,M, Viallon,V, Dossus,L, Gicquiau,A, Achaintre,D, Scalbert,A, Ferrari,P, Weiderpass,E, Gunter,MJ, Rinaldi,S] International Agency for Research on Cancer, Lyon, France. [Romieu,I] Centre for Research on Population Health, National Institute of Public Health, Cuernavaca, Mexico. [Onland-Moret,NC, van Gils,CH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Dahm,CC, Overvad,K] Department of Public Health, Aarhus University, Aarhus, Denmark. [Overvad,K] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Olsen,A, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] University of Copenhagen, Copenhagen, Denmark. [Fournier,A, Rothwell,JA, Severi,G] CESP, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Fournier,A, Severi,G] Gustave Roussy, Villejuif, France. [Kühn,T, Fortner,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Trichopoulou,A, Karakatsani,A, Martimianaki,G] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'M.P.Arezzo'Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Italian Institute for Genomic Medicine (IIGM), Turin, Italy. [Vineis,P] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Panico,S] Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy. [Nøst,TH, Sandanger,TM, Skeie,G] Department of Community Medicine, UiT the Arctic University of Norway, Tromso, Norway. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain. [Sánchez,MJ, Amiano,P, Huerta,JM, Ardanaz,E] CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Schmidt,JA, Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Riboli,E, Tsilidis,KK, Christakoudi,S] Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, Norfolk Place, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Christakoudi,S] MRC Centre for Transplantation, King’s College London, Great Maze Pond, London, SE1 9RT, UK, This work was funded by the French National Cancer Institute (grant number 2015-166). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), European Research Council (ERC-2009-AdG 232997), and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra, and the CERCA Program (Generalitat de Catalunya) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: 0301 basic medicine, Oncology, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Mass Spectrometry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Risk Factors, Estudios prospectivos, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], General Medicine, Metabolómica, Middle Aged, metabolomics, 3. Good health, Research Design, 030220 oncology & carcinogenesis, Cohort, Neoplasias de la mama, Female, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], Cohort study, Research Article, prospective study, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, breast cancer, Internal medicine, Cell Line, Tumor, General & Internal Medicine, medicine, Journal Article, Metabolomics, Humans, Prospective study, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, business.industry, lcsh:R, Case-control study, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings], Biomarkers
Abstract: BackgroundMetabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.MethodsA nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.ResultsAmong women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.ConclusionsThese findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.
Published: 2019
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19. Development and validation of circulating CA125 prediction models in postmenopausal women

Author: J. Ramón Quirós, N. Charlotte Onland-Moret, Anna Karakatsani, Marina Kvaskoff, Raina N. Fichorova, Pilar Amiano, Eva Lundin, Louise Hansen, Kathryn L. Terry, Sara Grioni, Kay-Tee Khaw, Leila Lujan-Barroso, Amalia Mattiello, Renée T. Fortner, Agnès Fournier, Linda J. Titus, Rudolf Kaaks, Sandra Colorado-Yohar, Anne Tjønneland, Timothy J. Key, Marc J. Gunter, Aurelio Barricarte, Shelley S. Tworoger, Laure Dossus, Britton Trabert, Naoko Sasamoto, Inger T. Gram, David C. Muller, Hanna Sartor, Bernard Rosner, Allison F. Vitonis, Francesca Mancini, Eleni Peppa, Valentina Fiano, María José Sánchez, Heiner Boeing, Daniel W. Cramer, Ana Babic, Hidemi S. Yamamoto, Rosario Tumino, Nicolas Wentzensen, Domenico Palli, Annika Idahl, Elisabete Weiderpass, Antonia Trichopoulou, Elio Riboli, Sasamoto, Naoko [0000-0002-4526-2181], Tjønneland, Anne [0000-0003-4385-2097], Tumino, Rosario [0000-0003-2666-414X], Apollo - University of Cambridge Repository, [Sasamoto,N, Vitonis,AF, Cramer,DW, Terry,KL] Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, USA. [Babic,A] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Rosner,BA] Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Fortner,RT, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Yamamoto,H, Fichorova,RN] Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA, USA.[Titus,LJ] Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center, Hanover, NH, USA. [Tjønneland,A, Hansen,L] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Kvaskoff,M, Fournier,A, Mancini,FR] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Kvaskoff,M, Mancini,FR] Gustave Roussy, Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Peppa,E, Karakatsani,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'Civic - M.P. Arezzo'Hospital, ASP, Ragusa, Italy. [Fiano,V] Unit of Cancer Epidemiology– CeRMS, Department of Medical Sciences, University of Turin, Turin, Italy. [Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. [Weiderpass,E, Gunter,M, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Gram,IT] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Lujan-Barroso,L] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L’ Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA). Universidad de Granada, Granada, Spain. [Sánchez,MJ, Colorado-Yohar,S, Barricarte,A, Amiano,P] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Colorado-Yohar,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Colorado-Yohar,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Barricarte,A] Navarra Public Health Institute, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Lundin,E] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Sartor,H] Department of Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden. [Sartor,H] Department of Translational Medicine, Lund University, Lund, Sweden. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Muller,D, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Trabert,B, Wentzensen,N] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, D.C, USA. [Tworoger,SS] Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA. [Tworoger,SS, Terry,KL] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Research reported in this publication was supported by U.S. National Institutes of Health under the following award numbers: R01 CA193965 (to K.L. Terry), R01 CA 158119 and R35 CA197605 (to D.W. Cramer), P01 CA087969 (to S.S. Tworoger), UM1 CA186107, R01 CA49449, UM1 CA176726, R01 CA67262, and supported in part by the intramural research program of the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten, The Cancer Research Foundation of Northern Sweden (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Antígeno Ca-125, Oncology, endocrine system diseases, medicine.medical_treatment, Càncer d'ovari, Ovarian neoplasms, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings], 0302 clinical medicine, Neoplasms, PROSTATE, 030212 general & internal medicine, CA-125, Early Detection of Cancer, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], 2. Zero hunger, RISK, Reproductive Biology, Biochemical markers, Obstetrics and Gynecology, Early detection, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Early diagnosis, female genital diseases and pregnancy complications, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Menopause, Postmenopause, Posmenopausia, 030220 oncology & carcinogenesis, Marcadors bioquímics, Biomarker (medicine), Female, Postmenopausal, Life Sciences & Biomedicine, Menopausa, medicine.medical_specialty, Neoplasias ováricas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Early Diagnosis::Early Detection of Cancer [Medical Subject Headings], BIOMARKERS, CA125, Ovarian cancer, Prediction model, Reproduktionsmedicin och gynekologi, lcsh:Gynecology and obstetrics, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Neoplasm::Antigens, Tumor-Associated, Carbohydrate::CA-125 Antigen [Medical Subject Headings], OVARIAN-CANCER, 03 medical and health sciences, Diagnóstico precoz, Internal medicine, Obstetrics, Gynecology and Reproductive Medicine, medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Sexual Development::Climacteric::Menopause::Postmenopause [Medical Subject Headings], lcsh:RG1-991, Aged, Hysterectomy, Science & Technology, business.industry, Research, Case-control study, CANCER SCREENING TRIAL, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Stepwise regression, Models, Theoretical, medicine.disease, VDP::Medical disciplines: 700, Detección precoz del cáncer, Check Tags::Female [Medical Subject Headings], CA-125 Antigen, Hormone therapy, business, Body mass index, LUNG
Abstract: Background Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. Methods We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses’ Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. Conclusions The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
Published: 2019
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20. Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study

Author: Anja M. Sedlmeier, Vivian Viallon, Pietro Ferrari, Laia Peruchet-Noray, Emma Fontvieille, Amina Amadou, Nazlisadat Seyed Khoei, Andrea Weber, Hansjörg Baurecht, Alicia K. Heath, Kostas Tsilidis, Rudolf Kaaks, Verena Katzke, Elif Inan-Eroglu, Matthias B. Schulze, Kim Overvad, Catalina Bonet, Esther Ubago-Guisado, María-Dolores Chirlaque, Eva Ardanaz, Aurora Perez-Cornago, Valeria Pala, Rosario Tumino, Carlotta Sacerdote, Fabrizio Pasanisi, Kristin B. Borch, Charlotta Rylander, Elisabete Weiderpass, Marc J. Gunter, Béatrice Fervers, Michael F. Leitzmann, Heinz Freisling, [Sedlmeier, Anja M. M.] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Weber, Andrea] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Baurecht, Hansjoerg] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Leitzmann, Michael F. F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Viallon, Vivian] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Ferrari, Pietro] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Peruchet-Noray, Laia] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Fontvieille, Emma] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Weiderpass, Elisabete] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Gunter, Marc J. J.] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Freisling, Heinz] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Peruchet-Noray, Laia] Univ Barcelona, Fac Med, Dept Clin Sci, Barcelona, Spain, [Amadou, Amina] Ctr Leon Berard, Dept Prevent Canc Environm, Lyon, France, [Fervers, Beatrice] Ctr Leon Berard, Dept Prevent Canc Environm, Lyon, France, [Amadou, Amina] INSERM, UMR1296 Radiat Def, Hlth, Environm, Lyon, France, [Fervers, Beatrice] INSERM, UMR1296 Radiat Def, Hlth, Environm, Lyon, France, [Seyed Khoei, Nazlisadat] Univ Vienna, Fac Life Sci, Dept Nutr Sci, Vienna, Austria, [Heath, Alicia K. K.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England, [Tsilidis, Kostas] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England, [Tsilidis, Kostas] Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina, Greece, [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany, [Katzke, Verena] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany, [Inan-Eroglu, Elif] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany, [Schulze, Matthias B. B.] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany, [Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark, [Bonet, Catalina] Catalan Inst Oncol ICO, Unit Nutr & Canc, Barcelona, Spain, [Bonet, Catalina] Bellvitge Biomed Res Inst IDIBELL, Canc Prevent & Palliat Care Program, Nutr & Canc Grp, Epidemiol,Publ Hlth, Barcelona, Spain, [Ubago-Guisado, Esther] Escuela Andaluza Salud Publ EASP, Granada, Spain, [Ubago-Guisado, Esther] Inst Invest Biosanitaria Ibs GRANADA, Granada, Spain, [Ubago-Guisado, Esther] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Chirlaque, Maria-Dolores] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Ardanaz, Eva] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Chirlaque, Maria-Dolores] Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Chirlaque, Maria-Dolores] Murcia Univ, IMIB Arrixaca, Murcia, Spain, [Ardanaz, Eva] IdiSNA, Navarra Publ Hlth Inst, Pamplona, Spain, [Perez-Cornago, Aurora] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England, [Pala, Valeria] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy, [Tumino, Rosario] AIRE ONLUS, Hyblean Assoc Epidemiol Res, Ragusa, Italy, [Sacerdote, Carlotta] Citta Salute & Sci Univ Hosp, Unit Canc Epidemiol, Turin, Italy, [Pasanisi, Fabrizio] Feder II Univ Hosp, Dept Clin Med & Surg, Clin Nutr Unit, Naples, Italy, [Borch, Kristin B. B.] UiT Arctic Univ Norway, Fac Hlth Sci, Dept Commun Med, Tromso, Norway, [Rylander, Charlotta] UiT Arctic Univ Norway, Fac Hlth Sci, Dept Commun Med, Tromso, Norway, French National Cancer Institute (l'Institut National du Cancer), International Agency for Research on Cancer (IARC), Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society (Denmark), Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (INSERM) (France), German Cancer Aid (Germany), German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy (Italy), Compagnia di San Paolo (Italy), National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS) (The Netherlands), Netherlands Cancer Registry (NKR) (The Netherlands), LK Research Funds (The Netherlands), Dutch Prevention Funds (The Netherlands), Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands), World Cancer Research Fund (WCRF) (The Netherlands), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain), Regional Government of Andalucia (Spain), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society (Sweden), Swedish Research Council (Sweden), County Council of Skane (Sweden), County Council of Vaesterbotten (Sweden), Cancer Research UK (United Kingdom), and Medical Research Council (United Kingdom)
Subjects: Cancer Research, Oncology, Height, Fat, Physical-activity, Obesity, Esophageal, Adenocarcinoma, Metaanalysis, Weight, Nutrition, Validity
Abstract: Background Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. Methods We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35–65 years at recruitment (1990–2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30–1.42) for endometrial cancer to 1.08 (1.03–1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02–1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03–1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99–1.01). Conclusions In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.
Published: 2022
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21. Osteoprotegerin and breast cancer risk by hormone receptor subtype: A nested case-control study in the EPIC cohort

Author: Miren Dorronsoro, Marc J. Gunter, Mathilde His, Helena Schock, Sabina Sieri, Maria Dolores Chirlaque, Aurélie Affret, Rudolf Kaaks, Elisabete Weiderpass, H. Bas Bueno-de-Mesquita, Philippos Orfanos, Melissa A. Merritt, Anne Tjønneland, Domenico Palli, J. Ramón Quirós, María José Sánchez, Theron Johnson, Danja Sarink, Eva Ardanaz, Antonio Agudo, Renée T. Fortner, Laure Dossus, Timothy J. Key, Kim Overvad, Rosario Tumino, Androniki Naska, Petra H.M. Peeters, Heiner Boeing, Amalia Mattiello, Anja Olsen, Sabina Rinaldi, Eiliv Lund, Antonia Trichopoulou, Carla H. van Gils, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Elio Riboli, Fulvio Ricceri, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, University Medical Center Utrecht, Imperial College Trust, [Fortner,RT, Sarink,D, Schock,H, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Affret,A, His,M, Boutron-Ruault,MC] Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. [Affret,A, Boutron-Ruault,MC] Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Naska,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.p.Arezzo' Hospital, ASP Ragusa, Italy. [Ricceri,F] Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy. [Ricceri,F] Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Peeters,PH, Van Gils,CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. [Weiderpass,E, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. [Weiderpass,E] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E] Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs. GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Research Institute CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Rinaldi,S, Dossus,L, Gunter,M] International Agency for Research on Cancer, Lyon, France., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain), the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).
Subjects: 0301 basic medicine, Oncology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Estrogen receptor, Progesterone receptor, Cohort Studies, 0302 clinical medicine, Breast cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B [Medical Subject Headings], Risk Factors, Prospective Studies, Prospective cohort study, Medicine(all), Osteoprotegerina, biology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, 11 Medical And Health Sciences, General Medicine, Middle Aged, Necrosi, 3. Good health, European Prospective Investigation into Cancer and Nutrition, RANK axis, RANKL, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Research Article, musculoskeletal diseases, medicine.medical_specialty, Receptores estrogénicos, Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Breast Neoplasms, Receptores de progesterona, Receptores de hormonas, Hormone receptor, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Càncer de mama, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Necrosis, 03 medical and health sciences, Osteoprotegerin, General & Internal Medicine, Internal medicine, Journal Article, medicine, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Case-control study, medicine.disease, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], 030104 developmental biology, Endocrinology, Case-Control Studies, Nested case-control study, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause [Medical Subject Headings], biology.protein, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: All Author: Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli and Rudolf Kaaks, Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER–, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: The associations between OPG and ER+ and ER– breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER– breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24–3.02]; ptrend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER– disease did not differ by menopausal status at blood collection (phet = 0.97), and we observed no heterogeneity by HT use at blood collection (phet ≥ 0.43) or age at breast cancer diagnosis (phet ≥ 0.30). Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER– breast cancer., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain); the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).
Published: 2017
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22. Diet quality scores and prediction of all-cause, cardiovascular and cancer mortality in a pan-european cohort study

Author: Lassale, Camille, Gunter, Marc J., Romaguera, Dora, Peelen, Linda M., Van der Schouw, Yvonne T., Beulens, Joline W. J., Freisling, Heinz, Muller, David C., Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Affret, Aurelie, Overvad, Kim, Dahm, Christina C., Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K., Katzke, Verena A., Kuehn, Tilman, Buijsse, Brian, Quiros, Jose-Ramon, Sanchez-Cantalejo, Emilio, Etxezarreta, Nerea, Maria Huerta, Jose, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay-Tee, Key, Timothy J., Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Boer, Jolanda M. A., Sonestedt, Emily, Nilsson, Lena Maria, Renstrom, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M., Riboli, Elio, Tzoulaki, Ioanna, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Lassale, Camille, Gunter, Marc J, Romaguera, Dora, Peelen, Linda M, Van der Schouw, Yvonne T, Beulens, Joline W. J, Freisling, Heinz, Muller, David C, Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron Ruault, Marie Christine, Affret, Aurélie, Overvad, Kim, Dahm, Christina C, Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K, Katzke, Verena A, Kühn, Tilman, Buijsse, Brian, Quirós, José Ramón, Sánchez Cantalejo, Emilio, Etxezarreta, Nerea, Huerta, José María, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay Tee, Key, Timothy J, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno de Mesquita, H. Ba, Boer, Jolanda M. A, Sonestedt, Emily, Nilsson, Lena Maria, Renström, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M, Riboli, Elio, Tzoulaki, Ioanna, [Lassale,C, Gunter,MJ, Romaguera,D, Tsilidis,KK, Riboli,E, Tzoulaki,I] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain. [Romaguera,D, Quirós,J, Sánchez-Cantalejo,E, Etxezarreta,N, Huerta,JM, Barricarte,A, Bonet,C] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Peelen,LM, Schouw,ITV, Beulens,JWJ, Moons,KGM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.[Freisling,H, Muller,DC, Ferrari,P, Huybrechts,I] International Agency for Research on Cancer, Lyon, France. [Fagherazz,G, Boutron-Ruault,M, Affret,A] Institut National de la Santé et de la Recherche Médicale, Center for Research in Epidemiology and Population, Health, Villejuif, France. Institut Gustave Roussy, Villejuif, France. Paris South University, Unité Mixte de Recherche, Villejuif, France. [Overvad,K, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Olsen,A, Roswall,N] Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Tsilidis,KK] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany. [Katzke,VA, Kühn,T] Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke German Institute of Human Nutrition, Potsdam, Germany. [Buijsse,B] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Quirós,R] Public Health Directorate, Asturias, Oviedo, Spain. [Sánchez-Cantalejo,E] Andalusian School of Public Health, Granada, Spain. [Etxezarreta,N] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Bonet,C] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Cambridge, United Kingdom. [Key,J] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. [Trichopoulou,A, Bamia,C, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Department of Preventive and Predictive Medicine, Foundation of the Carlo Besta Neurological Institute, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic MP Arezzo' Hospital, Ragusa, Italy. [Fasanelli,F] Human Genetics Foundation, Turin, Italy. [Bueno-de-Mesquita,HB, Boer,JMA] Center for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, Netherlands. [Sonestedt,E] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [Nilsson,LM, Renström,F] Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/ A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Male, humanos, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Social Sciences, Índice de masa corporal, Global Health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, distribución por sexos, Mathematical and Statistical Techniques, Sociology, Risk Factors, Neoplasms, Medicine and Health Sciences, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity [Medical Subject Headings], Public and Occupational Health, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], Estado Nutricional, estudios de cohortes, mediana edad, Factores de Riesgo, neoplasias, Medicine(all), Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Agricultural and Biological Sciences(all), dieta, Agriculture, Public Health, Global Health, Social Medicine and Epidemiology, Estudios Prospectivos, Plants, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Neoplasias, Näringslära, Cardiovascular Diseases, Hábitos alimenticios, estilo de vida, Physical Sciences, Medicine, Dieta, Female, Statistics (Mathematics), Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], General Science & Technology, Science, Estudios de cohortes, European Continental Ancestry Group, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], enfermedades cardiovasculares, Crops, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research and Analysis Methods, White People, Education, Fruits, Age Distribution, distribución por edades, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Anatomy::Cardiovascular System [Medical Subject Headings], Journal Article, factores de riesgo, Humans, Statistical Methods, Sex Distribution, Life Style, Educational Attainment, Nutrition, Sistema cardiovascular, Biochemistry, Genetics and Molecular Biology(all), Organisms, Biology and Life Sciences, Physical Activity, Nutrients, Actividad motora, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior::Food Habits [Medical Subject Headings], Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Hábito de Fumar, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, grupo de ascendencia continental europea, Mathematics, Forecasting, Crop Science
Abstract: Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors., The coordination of EPIC is financially supported by the European Commission (D-GSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC- Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Published: 2016
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23. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Author: María José Sánchez, Jennifer Ose, Antonia Trichopoulou, J. Ramón Quirós, Marc J. Gunter, Xavier Castellsagué, Carlotta Sacerdote, Inger T. Gram, H B As Bueno-de-Mesquita, Johanna Ekström, Ruth C. Travis, Joakim Dillner, Carmen Navarro, Silvia de Sanjosé, Annika Idahl, Renée T. Fortner, Domenico Palli, Noémie Travier, Amalia Mattiello, David Lindquist, Annika Steffen, Elisabete Weiderpass, Christian Munk, Kay-Tee Khaw, Aurelio Barricarte, Elio Riboli, Michael Pawlita, Petra H.M. Peeters, Valeria Pala, Eiliv Lund, Philippos Orfanos, Sabina Rinaldi, F. Xavier Bosch, Pagona Lagiou, Kim Overvad, Nerea Larrañaga, N. Margall, Sylvie Mesrine, Massimo Tommasino, Silvia Franceschi, Silvia Polidoro, Melissa A. Merritt, Tim Waterboer, Giovanna Masala, Agnès Fournier, Rosario Tumino, Esther Roura, Anne Tjønneland, Françoise Clavel-Chapelon, University Medical Center Utrecht, Imperial College Trust, [Roura,E, de Sanjosé,S, Bosch,FX, Castellsagué,X] Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Roura,E, Sánchez,MJ, Navarro,C, Barricarte,A, Larrañaga,N, Castellsagué,X] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Travier,N] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Waterboer,T, Pawlita,M] Division of Molecular Diagnostics of Oncogenic Infections (F020), Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.[Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Weiderpass, Dillner,J] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E, Gram,IT, Lund,E] Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Margall,N] Microbiology Department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain. [Dillner,J] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Munk,C] Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. [Palli,D, Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute–ISPO, Florence, Italy. [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Mesrine,S, Fournier,A] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Université Paris Sud, Villejuif, France.Institut Gustave Roussy, Villejuif, France. [Fortne,RT, Ose,J] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Steffen,A] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Lagiou,P, Orfanos,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, United States of America. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic—M.P. Arezzo' Hospital, Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, University of Turin, Turin, Italy. Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Turin, Italy. [Polidoro,S] Human Genetics Foundation (HuGeF), Turin, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.[Bueno-de-Mesquita,HB, Merritt,MA, Gunter,MJ, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.[Quirós,JR] Public Health Directorate, Asturias, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Barricarte,A] Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Larrañaga,N] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Basque Health Department, Bilbao, Spain. [Ekström,J] BBMRI.se Service Center for Southern Sweden, Lund University, Medicon Village, Lund, Sweden. [Lindquist,D] Department of Radiation Sciences, Umeå University, Umeå, Sweden. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Rinaldi,S, Tommasino,M, Franceschi,S] International Agency for Research on Cancer, Lyon, France., Funding: The work was partially supported by grants from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI08/1308, PI13/00053, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, RD12/0036/0018, and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695, 2009SGR939 and 2009SGR126, 2014SGR1077, 2014SGR2016). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and the Catalan Institute of Oncology, La Caixa (BM 06-130), RTICC-RD06/10091 (Spain), Danish Cancer Society (Denmark), Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC) and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom), and Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway).
Subjects: Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ::Cervical Intraepithelial Neoplasia [Medical Subject Headings], Oncology, Replacement therapy, Pathology and Laboratory Medicine, Antibodies, Viral, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pregnancy, Prospective Studies, lcsh:Science, Gonadal Steroid Hormones, education.field_of_study, Hormonal Therapy, Contraceptives, Humanos, Anticonceptivos, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Cohort studies, Science & Technology - Other Topics, Intreaepithelial neoplasia, Human, Cohort study, Oral, Human Papillomavirus Infection, medicine.medical_specialty, Càncer de coll uterí, Sexually Transmitted Diseases, Estudios retrospectivos, 03 medical and health sciences, Drug Therapy, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms [Medical Subject Headings], Neoplasias del cuello uterino, Humans, education, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Parity [Medical Subject Headings], Aged, Pharmacology, Gynecology, Cancer och onkologi, Science & Technology, Herpes Genitalis, Genitourinary Infections, Herpesvirus 2, lcsh:R, Case-control study, Biology and Life Sciences, Estrogens, medicine.disease, Hormones, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, Case-Control Studies, Cervical cancer, Medical Devices and Equipment, lcsh:Q, Intrauterine Devices, 0301 basic medicine, Glutathione-S-transferase, Viral Diseases, Human papillomavirus infection, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Herpesvirus 2, Human, lcsh:Medicine, Uterine Cervical Neoplasms, Chlamydia trachomatis, Cervical Cancer, Cohort Studies, Cervix cancer, Paridad, Medicine and Health Sciences, Viral, Non-U.S. Gov't, Prospective cohort study, Papillomaviridae, Reproductive History, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Reproductive Control Agents::Contraceptive Agents [Medical Subject Headings], Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Multidisciplinary, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Pharmaceutics, Research Support, Non-U.S. Gov't, Femenino, Drugs, Estudios de Casos y Controles, Middle Aged, humanities, Multidisciplinary Sciences, Infectious Diseases, Serology, Research Design, Hormonal therapy, Female, Research Article, Biotechnology, Adult, Risk, Papillomaviruses, Embarazo, General Science & Technology, Hormone Replacement Therapy, Urology, Population, Individual data, Research Support, Research and Analysis Methods, Cervical intraepithelial neoplasia, Antibodies, Contraceptives, Oral, Hormonal, Young Adult, Collaborative reanalysis, Internal medicine, Oral-contraceptives, MD Multidisciplinary, Journal Article, medicine, Multicentric case-control, Cervical Intraepithelial Neoplasia, Neoplasia Intraepitelial Cervical, Papil·lomavirus, Reproductive factors, Hormonal, business.industry, Carcinoma, Papillomavirus Infections, Cancers and Neoplasms, Chlamydia Infections, Uterine Cervical Dysplasia, Squamous Cell, Organisms::Viruses::DNA Viruses::Papillomaviridae [Medical Subject Headings], business, Gynecological Tumors, Follow-Up Studies
Abstract: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130) In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
Published: 2016

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

Author: Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J., Li, Qiyuan, Delgado, Melissa K., Lee, Janet M., Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Bandera, Elisa V., Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Børresen-Dale, Anne Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji Yeob, Claes, Kathleen B M, Cook, Linda S., Cox, Angela, Cramer, Daniel W., Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, Engel, Christoph, Lee, Eunjung, Evans, D. Gareth, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fridley, Brooke L., Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A., Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G., Glasspool, Rosalind, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Goode, Ellen L., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Heitz, Florian, Herzog, Josef, Høgdall, Estrid, Høgdall, Claus K., Hogervorst, Frans B L, Hollestelle, Antoinette, Hopper, John L., Hulick, Peter J., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jensen, Allan, John, Esther M., Johnson, Nichola, Kabisch, Maria, Kang, Daehee, Kapuscinski, Miroslav, Karlan, Beth Y., Khan, Sofia, Kiemeney, Lambertus A., Kjaer, Susanne Kruger, Knight, Julia A., Konstantopoulou, Irene, Kosma, Veli Matti, Kristensen, Vessela, Kupryjanczyk, Jolanta, Kwong, Ava, De La Hoya, Miguel, Laitman, Yael, Lambrechts, Diether, Le, Nhu, De Leeneer, Kim, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Lindblom, Annika, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lu, Karen, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Le Marchand, Loic, Margolin, Sara, Marme, Frederik, Massuger, Leon F A G, Matsuo, Keitaro, Mazoyer, Sylvie, McGuffog, Lesley, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Milne, Roger L., Montagna, Marco, Moysich, Kirsten B., Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Nord, Silje, Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olswold, Curtis, O'Malley, David, Orlow, Irene, Orr, Nick, Osorio, Ana, Park, Sue Kyung, Pearce, Celeste L., Pejovic, Tanja, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Poole, Elizabeth M., Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Rhenius, Valerie, Rhiem, Kerstin, Risch, Harvey A., Rodriguez, Gus, Rossing, Mary Anne, Rudolph, Anja, Salvesen, Helga B., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Sellers, Thomas A., Seynaeve, Caroline, Shah, Mitul, Shen, Chen Yang, Shu, Xiao Ou, Sieh, Weiva, Singer, Christian F., Sinilnikova, Olga M., Slager, Susan, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, Toland, Amanda Ewart, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tseng, Chiu Chen, Tung, Nadine, Tworoger, Shelley S., Vachon, Celine, Van Den Ouweland, Ans M W, Van Doorn, Helena C., Van Rensburg, Elizabeth J., Van't Veer, Laura J., Vanderstichele, Adriaan, Vergote, Ignace, Vijai, Joseph, Wang, Qin, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wu, Anna H., Yannoukakos, Drakoulis, Yoon, Sook Yee, Yu, Jyh Cherng, Zheng, Wei, Zheng, Ying, Khanna, Kum Kum, Simard, Jacques, Monteiro, Alvaro N., French, Juliet D., Couch, Fergus J., Freedman, Matthew L., Easton, Douglas F., Dunning, Alison M., Pharoah, Paul D., Edwards, Stacey L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Gayther, Simon A., Bowtell, David, DeFazio, Anna, Webb, Penny, Collonge-Rame, Marie Agnès, Damette, Alexandre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Ferrer, Sandra Fert, Bignon, Yves Jean, Uhrhammer, Nancy, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Adenis, Claude, Vénat-Bouvet, Laurence, Léone, Mélanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Verny-Pierre, Carole, Lasset, Christine, Bonadona, Valérie, Barjhoux, Laure, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Sokolowska, Johanna, Bronner, Myriam, Delnatte, Capucine, Bézieau, Stéphane, Mari, Véronique, Gauthier-Villars, Marion, Buecher, Bruno, Rouleau, Etienne, Golmard, Lisa, Moncoutier, Virginie, Belotti, Muriel, De Pauw, Antoine, Elan, Camille, Fourme, Emmanuelle, Birot, Anne Marie, Saule, Claire, Laurent, Maïté, Houdayer, Claude, Lesueur, Fabienne, Mebirouk, Noura, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Muller, Danièle, Fricker, Jean Pierre, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Mortemousque, Isabelle, Bressac-De-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brady, Angela, Barwell, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Cook, Jackie, Snape, Katie, Murray, Alex, McCann, Emma, Rookus, M. A., Van Leeuwen, F. E., Van Der Kolk, L. E., Schmidt, M. K., Russell, N. S., De Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., Van Deurzen, C. H M, Obdeijn, I. M., Van Asperen, C. J., Tollenaar, R. A E M, Van Cronenburg, T. C T E F, Kets, C. M., Ausems, M. G E M, Van Der Pol, C. C., Van Os, T. A M, Waisfisz, Q., Meijers-Heijboer, H. E J, Gómez-Garcia, E. B., Oosterwijk, J. C., Mourits, M. J., De Bock, G. H., Vasen, H. F., Siesling, S., Verloop, J., Overbeek, L. I H, Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Price, Melanie, NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Breast Cancer Research Trust, Instituto de Salud Carlos III, Lon V. Smith Foundation, Federal Ministry of Education & Research (Alemania), Finlands Akademi (Finlandia), United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Canadian Institutes of Health Research, Ministère de Économie, Innovation et Exportation (Canadá), Ministry of Higher Education (Malasia), National Medical Research Council (Singapur), University of Oulu (Finlandia), Yorkshire Cancer Research, Hellenic Cooperative Oncology Group, California Cancer Research Program, Danish Cancer Society, Ministry of Science and Higher Education (Polonia), Asociación Española Contra el Cáncer, University of Kansas. Cancer Center (Estados Unidos), Hungarian Research Grants, Norwegian EEA Financial Mechanism, Canadian Breast Cancer Network, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Congressionally Directed Medical Research Programs (Estados Unidos), NRG Oncology National (Estados Unidos), Unión Europea. Comisión Europea. 7 Programa Marco, Medical Oncology, Obstetrics & Gynecology, Clinical Genetics, 1 Department of Preventive Medicine, Keck School of MediCenter, Kansas City, Kansas 66160, USA. 90 Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel. 91 Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, Pisa 56126, Italy. 92 UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, California 90024, USA. 93 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 94 Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK. 95Women’s Cancer, UCL EGA Institute for Women’s Health, London WC1E 6AU, UK. 96 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. 97 Cancer Research UK Clinical Trials Unit, The BeatsonWest of Scotland Cancer Centre, Glasgow G12 0YN, UK. 98 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. 99 Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Que´bec H3A 1A1, Canada. 100 Department of Medicine, McGill University, Montreal, Que´bec H3A 1A1, Canada. 101 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. 102 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55902, USA. 103 Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 104Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 105 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA. 106 Department of Genetics and Pathology, Pomeranian Medical University, 70-204 Szczecin, Poland. 107 Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, 94805 Villejuif, France. 108 University Paris- Sud, 91405 Villejuif, France. 109 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 110 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark. 111 Department of Oncology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK. 112 Saw Swee Hock School of Public Health, National University of Singapore Singapore 119077, Singapore. 113 Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia. 114 Cancer Research Initiatives Foundation, Subang Jaya, 47500 Selangor, Malaysia. 115 Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136 Essen, Germany. 116 Department of Gynecology and Gynecologic Oncology, Dr Horst Schmidt Kliniken Wiesbaden, 65199 Wiesbaden, Germany. 117 Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte California 91010, USA. 118 Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, 2730 Copenhagen, Denmark. 119 Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. 120 Department of Gynecology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark. 121 Family Cancer Clinic, Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands. 122 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 Rotterdam, The Netherlands. 123 Center for Medical Genetics, NorthShore University Health System, Evanston, Illinois 60201, USA. 124 N.N. Petrov Institute of Oncology, St Petersburg 197758, Russia. 125 Lombardi Comprehensive Cancer Center, Georgetown University, Washington District of Columbia 20057, USA. 126 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi 464-8681, Japan. 127 State Research Institute Centre for Innovative Medicine, LT-01102 Vilnius, Lithuania. 128 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA. 129 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 08826, Korea. 130 Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia. 131Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 132 Radboud University Medical Centre, Radboud Institute for Health Sciences, 6500 Nijmegen, The Netherlands. 133 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. 134 Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. 135 Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, 70210 Kuopio, Finland. 136 Cancer Center, Kuopio University Hospital, 70210 Kuopio, Finland. 137 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland. 138 Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, 1478 Oslo, Norway. 139 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. 140 Department of Surgery, The University of Hong Kong, Hong Kong, China. 141Vesalius Research Center, VIB, 3000 Leuven, Belgium. 142 Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. 143 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 144 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK. 145 Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 146 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), 20133 Milan, Italy. 147 University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. 148 Department of Oncology - Pathology, Karolinska Institutet, SE- 171 77 Stockholm, Sweden. 149 National Center for Tumour Diseases, University of Heidelberg, 69117 Heidelberg, Germany. 150 Department of Gynaecology, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 151 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka 812-8582, Japan. 152 Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria 3004, Australia. 153 Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. 154 Division of Gynaecology and Obstetrics, Technische Universita¨t Mu¨nchen, 81675 Munich, Germany. 155 Department of Human Genetics, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 156 Immunology and Molecular Oncology Unit, Instituto Oncologico Veneto IOV, IRCCS, 35128 Padua, Italy. 157 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 158 Institute of Population Health, University of Manchester, Manchester M13 9PL, UK. 159 Laboratory Medicine Program, University Health Network, Toronto, Ontario M5G 1L7, Canada. 160 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada. 161 The University of Texas School of Public Health, Houston, Texas 77030, USA. 162 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA. 163 Department of Medicine and Genetics, University of California, San Francisco, California 94143, USA. 164 Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 165 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 166 Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary. 167 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA. 168 The Ohio State University and the James Cancer Center, Columbus, Ohio 43210, USA. 169 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York 10017, USA. 170 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28019 Madrid, Spain. 171 Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain. 172 Department of Surgery, Seoul National University College of Medicine, Seoul, 03080 Korea. 173 Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. 174 Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. 175 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, 16 20139 Milan, Italy. 176 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. 177 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida 33606, USA. 178 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 179 Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts 02115, USA. 180 Laboratory of Cancer Genetics and Tumour Biology, Northern Finland Laboratory Centre NordLab, FI-90014 Oulu, Finland. 181 Laboratory of Cancer Genetics and Tumour Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland. 182 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT),cine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA. 2 Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 3 QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia. 4 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 5 Medical College, Xiamen University, Xiamen 361102, China. 6 Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 7 Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki 00029 HUS, Finland. 8 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario Canada, M5G 1X5. 9 Department of Molecular Genetics, University of Toronto, Toronto, OntarioCanada, M5S 1A8. 10 Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California 92697, USA. 11 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany. 12 University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 13 Department of Oncology, Karolinska University Hospital, Stockholm 171 77, Sweden. 14 Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA. 15 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan 20141, Italy. 16 Department of Pathology, Landspitali University Hospital and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik 600169- 2039, Iceland. 17 University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen 91054, Germany. 18 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid E-28029, Spain. 19 Centro de Investigacio´n en Red de Enfermedades Raras, Valencia 28029, Spain. 20 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710, USA. 21 Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 22 Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway. 23 Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway. 24 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland. 25 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. 26 International Epidemiology Institute, Rockville, Maryland 20850, USA. 27 Gynaecology Research Unit, Hannover Medical School, Hannover D-30625, Germany. 28 Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark. 29 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. 30 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 31 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 32 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo N-0310, Norway. 33 K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo N-0310, Norway. 34 Dr Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart D-70376, Germany. 35 University of Tu¨bingen, Tu¨bingen 72074, Germany. 36 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 37 International Agency for Research on Cancer, Lyon 69008, France. 38 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 39 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. 40 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d’Investigacio´ Biome`dica de Girona), Catalan Institute of Oncology, Girona 08908, Spain. 41 Department of Surgery, National University Health System, Singapore 119077, Singapore. 42 Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 43 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg 69120, Germany. 44 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00029 HUS, Finland. 45 Department of Pathology, Helsinki University Central Hospital, Helsinki 00029, Finland. 46 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. 47 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigacio´n Sanitaria del Hospital Clı ´nico San Carlos), Madrid 28040, Spain. 48 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia. 49 Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo 14263, New York, USA. 50 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 51 University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany. 52 Unite´ de recherche en sante´ des populations, Centre des maladies du sein Descheˆnes-Fabia, Centre de recherche FRSQ du Centre hospitalier affilie´ universitaire de Que´bec, Que´bec City, Que´bec Canada, G1J 1Z4. 53 Cancer Research Institute, Seoul National University, Seoul 08826, Korea. 54 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. 55 Center for Medical Genetics, Ghent University, Ghent 9000, Belgium. 56 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA. 57 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield S10 2TN, UK. 58 Harvard HT Chan School of Public Health, Boston, Massachusetts 02115, USA. 59 Obstetrics and Gynecology Epidemiology Center, Brigham andWomen’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 60 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK. 61 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-115, Poland. 62 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-171 77, Sweden. 63 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 64 INSERM U1052, CNRS UMR5286, Universite´ Lyon, Centre de Recherche en Cance´rologie de Lyon, Lyon 69373, France. 65 Department of Pathology and Laboratory Diagnostics the Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology,Warsaw 44-101, Poland. 66 Department of Pathology, Leiden University Medical Center, Leiden 2333, The Netherlands. 67 Department of Human Genetics, Leiden University Medical Center, Leiden 2333, The Netherlands. 68 Oncogenetics Group, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO) and Universitat Auto`noma de Barcelona, Barcelona, 186 Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, 50931 Cologne, Germany. 187Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut 06510, USA. 188Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois 60201, USA. 189 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. 190Department of Epidemiology, University of Washington, Seattle, Washington 98109, USA. 191National Cancer Institute, Bangkok 10400, Thailand. 192 Research Oncology, Guy’s Hospital, King’s College London, London SE1 9RT, UK. 193Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. 194 Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina 27710, USA. 195Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands. 196Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, 50676 Cologne, Germany. 197 Center for Integrated Oncology, University Hospital of Cologne, 50676 Cologne, Germany. 198 Center for Molecular Medicine, University Hospital of Cologne, 50676 Cologne, Germany. 199 Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, 50676 Cologne, Germany. 200 Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. 201 School of Public Health, China Medical University, Taichung 404, Taiwan. 202Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford California 94305, USA. 203 Unite´ Mixte de Ge´ne´tique Constitutionnelle des Cancers Fre´quents, Hospices Civils de Lyon – Centre Le´on Be´rard, Lyon 69008, France. 204 INSERM U1052, CNRS UMR5286, Universite´ Lyon 1, Centre de Recherche en Cance´rologie de Lyon, Lyon 69003, France. 205Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia. 206Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linko¨ping University, 581 83 Linko¨ping, Sweden. 207 Institut Curie, Department of Tumour Biology, Paris, France, Institut Curie, INSERM U830, 75248 Paris, France. 208Universite´ Paris Descartes, Sorbonne Paris Cite´, 75270 Paris, France. 209 Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany. 210Department of Genetics, Portuguese Oncology Institute, Porto 4200-072, Portugal. 211 Biomedical Sciences Institute (ICBAS), Porto University, Porto 4099-002, Portugal. 212Department of Epidemiology, Mailman School of Public Health, Columbia University, New York 10027, USA. 213Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark. 214UO Anatomia Patologica, Ospedale di Circolo-Universita` dell’Insubria, 21100 Varese, Italy. 215 Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia. 216 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), 64 - 35128 Padua, Italy. 217Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA. 218Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK. 219 Institute of Human Genetics, Pontificia Universidad Javeriana, Cra. 7 #40-62 Bogota, Colombia. 220Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 221Department of Clinical Genetics, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands. 222Department of Gynecology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands. 223Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 224University Hospital Ulm, 89069 Ulm, Germany. 225Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Maryland 20892, USA. 226 Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 227 Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, Athens 153 10, Greece. 228 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 47500 Subang Jaya, Malaysia. 229 University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Malaysia. 230Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114 Taiwan. 231 Shanghai Center for Disease Control and Prevention, Shanghai, China. 232 Cancer Epidemiology Program, Division of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. 233Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. 234 Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. 235 Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. 236 Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK. 237 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia. 238 Department of Gynaecological Oncology, Westmead Institute for Cancer Research, Westmead Hospital Westmead, New South Wales 2145, Australia., Tyrer, Jonathan [0000-0003-3724-4757], Dennis, Joe [0000-0003-4591-1214], Rhenius, Valerie [0000-0003-4215-3235], Song, Honglin [0000-0001-5076-7371], Wang, Jean [0000-0002-9139-0627], Easton, Douglas [0000-0003-2444-3247], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Quality of care, Anesthesiology, Human genetics, CCA - Cancer biology, and VU University medical center
Subjects: endocrine system diseases, Messenger, IDENTIFIES 3, MODIFIERS, Brjóstakrabbamein, BRCA2 MUTATION CARRIERS, Medicine and Health Sciences, GWAS, INVESTIGATORS, African Continental Ancestry Group, Asian Continental Ancestry Group, Breast Neoplasms, Chromosomes, Human, Pair 19, Female, Genome-Wide Association Study, Genotype, Humans, Ovarian Neoplasms, RNA, Messenger, Alleles, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, skin and connective tissue diseases, COMMON VARIANTS, EPITHELIAL-CELLS, Single Nucleotide, female genital diseases and pregnancy complications, NAF12, Medical Genetics, Human, endocrine system, Science, Chromosomes, Human, Pair 19/genetics, Black People, Breast Neoplasms/genetics, Chromosomes, Article, Ovarian Neoplasms/genetics, SDG 3 - Good Health and Well-being, Asian People, REVEALS, Polymorphism, GENOME-WIDE ASSOCIATION, Krabbamein, Medicinsk genetik, Cancer och onkologi, Pair 19, Arfgengi, GENE, Eggjastokkar, Cancer and Oncology, RNA, BRCA1 Protein/genetics
Abstract: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P, A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.
Published: 2016
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25. A novel pathway down-modulating T cell activation involves HPK-1–dependent recruitment of 14-3-3 proteins on SLP-76

Author: Julien Fourtane, Olivier Schwartz, Oreste Acuto, Florent Carrette, Mogjiborahman Salek, Britta Jungwirth, Nathalie Sol-Foulon, Benjamin Montagne, Vincenzo Di Bartolo, Frédérique Michel, Wolf D. Lehmann, Immunologie Moléculaire, Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Central Spectroscopy German Cancer Research Center (DKFZ) (CENTRAL SPECTROSCOPY), German Cancer Research Center DKFZ, Virus et Immunité, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Central Spectroscopy, German Cancer Research Center, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the Institut Pasteur, the CNRS, the Association pour la Recherche sur le Cancer, the Ligue Contre le Cancer-Comité Ile-de-France, and the European Union (MUGEN Network of Excellence, contract no. LSGH-CT-2005-005203)., European Project: 39516,MUGEN, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: genetic structures, T-Lymphocytes, [SDV]Life Sciences [q-bio], Immunology, Down-Regulation, Protein Serine-Threonine Kinases, Biology, Lymphocyte Activation, Jurkat cells, Article, Phosphorylation cascade, Serine, Jurkat Cells, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chlorocebus aethiops, Animals, Humans, Immunology and Allergy, Protein phosphorylation, Phosphorylation, Adaptor Proteins, Signal Transducing, 030304 developmental biology, 0303 health sciences, T-cell receptor, Tyrosine phosphorylation, Articles, Phosphoproteins, equipment and supplies, Molecular biology, eye diseases, Cell biology, 14-3-3 Proteins, chemistry, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, COS Cells, sense organs, Signal transduction, Protein Binding, Signal Transduction, 030215 immunology
Abstract: International audience; The SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is a pivotal element of the signaling machinery controlling T cell receptor (TCR)-mediated activation. Here, we identify 14-3-3epsilon and zeta proteins as SLP-76 binding partners. This interaction was induced by TCR ligation and required phosphorylation of SLP-76 at serine 376. Ribonucleic acid interference and in vitro phosphorylation experiments showed that serine 376 is the target of the hematopoietic progenitor kinase 1 (HPK-1). Interestingly, either S376A mutation or HPK-1 knockdown resulted in increased TCR-induced tyrosine phosphorylation of SLP-76 and phospholipase C-gamma1. Moreover, an SLP-76-S376A mutant induced higher interleukin 2 gene transcription than wild-type SLP-76. These data reveal a novel negative feedback loop involving HPK-1-dependent serine phosphorylation of SLP-76 and 14-3-3 protein recruitment, which tunes T cell activation.
Published: 2007
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26. Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

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

Author: Carla H. van Gils, E. Riboli, Christos Tsironis, Anne-Claire Vergnaud, H. Bas Bueno-de-Mesquita, Laureen Dartois, José Ramón Quirós, Veronika Fedirko, Pietro Ferrari, Teresa Norat, Pagona Lagiou, Christina C. Dahm, Giovanna Masala, Timothy J. Key, Mark J. Gunter, Maria Wennberg, Kay-Tee Khaw, Verena Katzke, Petra H.M. Peeters, Aurelio Barricarte, Heather Ward, Nicholas J. Wareham, Anne Tjønneland, Lena Maria Nilsson, Bodil Ohlsson, Valeria Pala, Laure Dossus, Antonia Trichopoulou, Tilman Kühn, Heiner Boeing, Elisabete Weiderpass, Petra A. Wark, M. Dorronsoro, Carmen Navarro, Camilla Plambeck Hansen, Genevieve Buckland, Salvatore Panico, Marie-Christine Boutron-Ruault, María José Sánchez, Paolo Vineis, Peter D. Siersema, Karin Jirström, Dora Romaguera, Rosario Tumino, Mazda Jenab, Romaguera, Dora, Ward, Heather, Wark, Petra A, Vergnaud, Anne Claire, Peeters, Petra H, van Gils, Carla H, Ferrari, Pietro, Fedirko, Veronika, Jenab, Mazda, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Hansen, Camilla Plambeck, Dahm, Christina Catherine, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Navarro, Carmen, Barricarte, Aurelio, Key, Timothy J, Trichopoulou, Antonia, Tsironis, Christo, Lagiou, Pagona, Masala, Giovanna, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Ohlsson, Bodil, Jirström, Karin, Wennberg, Maria, Nilsson, Lena M, Weiderpass, Elisabete, Kühn, Tilman, Katzke, Verena, Khaw, Kay Tee, Wareham, Nick J, Tjønneland, Anne, Boeing, Heiner, Quirós, José R, Gunter, Marc J, Riboli, Elio, Norat, Teresa, Department of Medical and Clinical Genetics, Medicum, BMC, BMC, Department of Epidemiology and Public Health, Imperial College London, Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, CIBER Fisiopatología de la Obesidad y Nutrición ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Department of Primary Care and Public Health, Department of Epidemiology, University Medical Center [Utrecht]-Julius Center for Health Sciences and Primary Care, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Emory University [Atlanta, GA]-Rollins School of Public Health-Winship Cancer Institute, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Section for Epidemiology, Aarhus University [Aarhus], Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Murcia Regional Health Council [Murcia], Department of Health and Social Sciences, Universidad de Murcia, Navarre Public Health Institute, Cancer Epidemiology Unit, University of Oxford, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, Department of Hygiene, Epidemiology and Medical Statistics, Harvard School of Public Health, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Cancer Registry and Histopathology Unit, Department of Oncology-Civile - M.P.Arezzo Hospital, Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II = Università degli studi di Napoli Federico II, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], Division of Internal Medicine, Skane University Hospital [Malmo], Lund University [Lund]-Lund University [Lund], Division of Oncology and Pathology, Lund University [Lund], Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Arctic Research Centre, Department of Community Medicine, The Arctic University of Norway [Tromsø, Norway] (UiT), Department of Research, Cancer Registry of Norway, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Clinical Gerontology Unit, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Danish Cancer Society Research Center, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Public Health Directorate, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Oxford [Oxford], Università degli studi di Torino (UNITO), University of Naples Federico II, University of Malaya, The Arctic University of Norway, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, [Romaguera,D, Ward,H, Vergnaud,A, Peeters,PH, Vineis,P, Bueno-de-Mesquita,HB, Gunter, MJ, Riboli,E, Norat,T] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Romaguera,D] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Wark,PA] Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK. [Peeters,PH, Gils, CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ferrari,P, Jenab,M] International Agency for Cancer Research (IARC), Lyon CEDEX, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA. [Fedirko,V] Winship Cancer Institute, Emory University, Atlanta, USA. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health (CESP), Vaillant, Villejuif, Cedex, France. [Boutron-Ruault,M, Dartois,L] Univ Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L] Gustave Roussy, Villejuif, France. [Hansen,CP, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Dorronsoro,M, Navarro,C, Barricarte,A] CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Campus Universitario de Espinardo, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford UK. [Trichopoulou,A, Tsironis,C] Hellenic Health Foundation, Athens, Greece . [Trichopoulou,A, Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic – M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P] HuGeF Foundation, Turin, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven The Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skane University Hospital, Malmo, Lund University, Lund, Sweden. [Jirström,K] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Wennberg,M] Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Nilsson,LM] Arctic Research Centre, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, ISM - Universitetet i Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Majorstuen Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Folkhälsan Research Center, Biomedicum 1, University of Helsinki, Helsinki, Finland. [Kühn,T, Katzke,V] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology Im Neuenheimer Feld 581, Heidelberg, Germany. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Quirós,JR] Public Health Directorate, Oviedo Asturias, Spain., This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economía y Competitividad, Spain and European Regional Development Fund, RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), Danish Cancer Society, Catalan Institute of Oncology, Spain, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain, Cancer Research UK, Medical Research Council, United Kingdom, The Hellenic Health Foundation, Greece, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Helga—Nordic Center of Excellence Programme in Nutrition and Health, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l'Education Romaguera et al. BMC Medicine (2015) 13:107 Page 10 of 12 Nationale (MGEN), France, 3 M Co., France, Gustave Roussy Institute (IGR), France, and and General Councils of France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, physical activity, 0302 clinical medicine, estudios prospectivos, Prospective Studies, estudios de cohortes, mediana edad, Aged, 80 and over, anciano, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, Hazard ratio, COLON-CANCER, General Medicine, adulto, 3. Good health, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, estilo de vida, Cohort, Dieta, Estilo de Vida, RESEARCH FUND/AMERICAN INSTITUTE, Cohort study, Human, medicine.medical_specialty, Concordance, European Continental Ancestry Group, DIAGNOSIS, incidencia, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Neoplasias Colorrectales, BREAST-CANCER, Humans, Life Style, Aged, Cancer prevention, Proportional hazards model, Physical activity, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], weight, LIFE-STYLE FACTORS, Colorectal cancer, REPRODUCTIVE HISTORY, Prospective Studie, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Proportional Hazards Model, grupo de ascendencia continental europea, Estudios de Cohortes, Gerontology, cumplimiento del paciente, Survival, modelos de riesgos proporcionales, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, [SDV]Life Sciences [q-bio], humanos, Colorectal Neoplasm, Alcohol consumption, Breast cancer, Prospective study, Named Groups::Persons::Survivors [Medical Subject Headings], Cohort Studies, 030212 general & internal medicine, Prospective cohort study, Non-U.S. Gov't, 2. Zero hunger, Medicine(all), RISK, Nutrition and Dietetics, Healthy lifestyle, Diet, Weight, Research Support, Non-U.S. Gov't, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, NUTRITION, Female, Colorectal Neoplasms, Research Article, Adult, neoplasias colorrectales, 3122 Cancers, RECREATIONAL PHYSICAL-ACTIVITY, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], colorectal cancer, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, survival, Sobrevivientes, healthy lifestyle, Internal medicine, medicine, Journal Article, Proportional Hazards Models, Actividad Motora, business.industry, Physical fitness, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Other Clinical Medicine, 3121 General medicine, internal medicine and other clinical medicine, Patient Compliance, Cohort Studie, business, diet, Condició física
Abstract: Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend, We would like to acknowledge the contribution of all participants in the study. This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economia y Competitividad, Spain and European Regional Development Fund; RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Catalan Institute of Oncology, Spain; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra; ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain; Cancer Research UK; Medical Research Council, United Kingdom; The Hellenic Health Foundation, Greece; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Fondazione-Istituto Banco Napoli, Italy; Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Helga-Nordic Center of Excellence Programme in Nutrition and Health; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Generale de l'Education Nationale (MGEN), France; 3 M Co., France; Gustave Roussy Institute (IGR), France; and General Councils of France.
Published: 2014
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28. Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization

Author: Esther Clavero, José Manuel Sanchez-Maldonado, Angelica Macauda, Rob Ter Horst, Belém Sampaio-Marques, Artur Jurczyszyn, Alyssa Clay-Gilmour, Angelika Stein, Michelle A. T. Hildebrandt, Niels Weinhold, Gabriele Buda, Ramón García-Sanz, Waldemar Tomczak, Ulla Vogel, Andrés Jerez, Daria Zawirska, Marzena Wątek, Jonathan N. Hofmann, Stefano Landi, John J. Spinelli, Aleksandra Butrym, Abhishek Kumar, Joaquín Martínez-López, Sara Galimberti, María Eugenia Sarasquete, Edyta Subocz, Elzbieta Iskierka-Jażdżewska, Graham G. Giles, Malwina Rybicka-Ramos, Marcin Kruszewski, Niels Abildgaard, Francisco García Verdejo, Pedro Sánchez Rovira, Miguel Inacio da Silva Filho, Katalin Kadar, Małgorzata Razny, Wendy Cozen, Matteo Pelosini, Manuel Jurado, Parveen Bhatti, Marek Dudzinski, Agnieszka Druzd-Sitek, Enrico Orciuolo, Yang Li, Aaron D. Norman, Jan Maciej Zaucha, Rui Manuel Reis, Miroslaw Markiewicz, Juan José Rodríguez Sevilla, Vibeke Andersen, Krzysztof Jamroziak, Kari Hemminki, Sonja I. Berndt, Vicent Rajkumar, Grzegorz Mazur, Shaji K. Kumar, Paula Ludovico, Arnon Nagler, Stephen J. Chanock, Charles Dumontet, Mitchell J. Machiela, Judit Varkonyi, Nicola J. Camp, Elad Ziv, Annette Juul Vangsted, Elizabeth E. Brown, Daniele Campa, Celine M. Vachon, Mihai G. Netea, Federico Canzian, Asta Försti, Juan Sainz, Institut Català de la Salut, [Clavero E] Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Sanchez-Maldonado JM] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain. Instituto de Investigación Biosanataria IBs, Granada, Granada, Spain. [Macauda A] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Ter Horst R] Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, GA Nijmegen, The Netherlands. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. [Sampaio-Marques B] Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. [Jurczyszyn A] Plasma Cell Dyscrasias Center, Department of Hematology, Jagiellonian University Medical College, Kraków, Poland. [Jerez A] Experimental Hematology Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: fenómenos fisiológicos celulares::muerte celular::autofagia [FENÓMENOS Y PROCESOS], Cell Physiological Phenomena::Cell Death::Autophagy [PHENOMENA AND PROCESSES], Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Protein Disorders::Paraproteinemias::Hemic and Lymphatic Diseases::Hematologic Diseases::Multiple Myeloma [DISEASES], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Mieloma múltiple - Aspectes genètics, General Medicine, Biological Factors::Biomarkers [CHEMICALS AND DRUGS], Catalysis, factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS], Computer Science Applications, multiple myeloma, autophagy, genetic variants, genetic susceptibility, Inorganic Chemistry, All institutes and research themes of the Radboud University Medical Center, Autofàgia, Marcadors bioquímics, Other subheadings::Other subheadings::/genetics [Other subheadings], Physical and Theoretical Chemistry, enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos de las proteínas sanguíneas::paraproteinemias::enfermedades hematológicas y linfáticas::enfermedades hematológicas::mieloma múltiple [ENFERMEDADES], Molecular Biology, Spectroscopy
Abstract: Autophagy; Genetic variants; Multiple myeloma Autofagia; Variantes genéticas; Mieloma múltiple Autofàgia; Variants genètiques; Mieloma múltiple Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways. This work was supported by the European Union’s Horizon 2020 research and innovation program, N° 856620 and by grants from the Instituto de Salud Carlos III and FEDER (Madrid, Spain; PI17/02256 and PI20/01845), Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER (PY20/01282), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]), and from National Cancer Institute of the National Institutes of Health under award numbers: R01CA186646, U01CA249955 (EEB). This work was also funded d by Portuguese National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020 and by the project NORTE-01-0145-FEDER-000055, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).
Published: 2023

29. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author: Broséus, Julien, Hergalant, Sébastien, Vogt, Julia, Tausch, Eugen, Kreuz, Markus, Dartigeas, Caroline, Schneider, Christof, Mottok, Anja, Roos-Weil, Damien, Quinquenel, Anne, Moulin, Charline, Ott, German, Blanchet, Odile, Tomowiak, Cécile, Lazarian, Grégory, Rouyer, Pierre, Tournilhac, Olivier, Bernhart, Stephan H., Chteinberg, Emil, Gauchotte, Guillaume, Lomazzi, Sandra, Chapiro, Elise, Nguyen-Khac, Florence, Chery, Céline, Davi, Frédéric, Hunault, Mathilde, Houlgatte, Rémi, Rosenwald, Andreas, Delmer, Alain, Meyre, David, Béné, Marie-Christine, Thieblemont, Catherine, Lichter, Peter, Guéant, Jean-Louis, Guièze, Romain, Martin-Subero, José Ignacio, Ammerpohl, Ole, Cymbalista, Florence, Feugier, Pierre, Siebert, Reiner, Stilgenbauer, Stephan, Publica, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Universitätsklinikum Ulm - University Hospital of Ulm, Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service d'Hématologie [CHRU Nancy], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre de Ressources Biologiques - [Nancy] (CRB Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Service d'hématologie [Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institute of pathology [Würzburg], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), and Hergalant, Sébastien
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Epigenomics, Chronic lymphocytic leukaemia, Lymphoma, B-Cell, B-Zell-Lymphom, biostatistics, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, General Biochemistry, Genetics and Molecular Biology, integrative genomics, DDC 570 / Life sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:570, ddc:610, Transcriptomics, Epigenetik, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Multidisciplinary, B-cell lymphoma, Gene Expression Profiling, Computational Biology, classifiers, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, bioinformatics, General Chemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computational biology and bioinformatics, DLBCL, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chronic lymphocytic leukemia, Epigenetics, Richter syndrome, DDC 610 / Medicine & health, CLL
Abstract: Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We characterize 58 primary human RS samples by genome-wide DNA methylation and whole-transcriptome profiling. Our comprehensive approach determines RS DNA methylation profile and unravels a CLL epigenetic imprint, allowing CLL-RS clonal relationship assessment without the need of the initial CLL tumor DNA. DNA methylation- and transcriptomic-based classifiers were developed, and testing on landmark DLBCL datasets identifies a poor-prognosis, activated B-cell-like DLBCL subset in 111/1772 samples. The classification robustly identifies phenotypes very similar to RS with a specific genomic profile, accounting for 4.3-8.3% of de novo DLBCLs. In this work, RS multi-omics characterization determines oncogenic mechanisms, establishes a surrogate marker for CLL-RS clonal relationship, and provides a clinically relevant classifier for a subset of primary “RS-type DLBCL” with unfavorable prognosis., publishedVersion
Published: 2023
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30. The rotate-plus-shift C-arm trajectory. Part I. Complete data with less than 180° rotation

Author: Kachelrieß, Marc [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120 (Germany)]
Published: 2016
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31. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Anne Kirstine Eriksen, Elio Riboli, José María Huerta, H. Bas Bueno-de-Mesquita, Giovanna Masala, Núria Sala, Anne Tjønneland, Anika Hüsing, Rudolf Kaaks, Sara Grioni, Anne M. May, Fanny Artaud, Antonia Trichopoulou, Pilar Amiano, Eleni Peppa, Marc J. Gunter, Timothy J. Key, Aurelio Barricarte Gurrea, Jonna Berntsson, Anna Karakatsani, Mazda Jenab, Elisabete Weiderpass, Isabel Drake, Christina C. Dahm, Torkjel M. Sandanger, Bethany Van Guelpen, Robin Reichmann, María José Sánchez, Guri Skeie, Konstantinos K. Tsilidis, Gianluca Severi, Carlotta Sacerdote, Sjoerd G. Elias, José Ramón Quirós, Marie-Christine Boutron-Ruault, Salvatore Panico, Krasimira Aleksandrova, Rosario Tumino, Sophia Harlid, Elom K. Aglago, [Aleksandrova,K, Reichmann,R] Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Aleksandrova,K, Reichmann,R] Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. [Aleksandrova,K] Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. [Kaaks,R, Hüsing,A] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jenab,M, Weiderpass,E, Aglago,EK, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Cross,AJ, Tsilidis,KK, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Dahm,CC] Department of Public Health, Aarhus University, Aarhus, Denmark. [Eriksen,AK, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Artaud,F, Boutron-Ruault,MC, Severi,G] CESP, Faculté de Medicine, Université Paris-Saclay, Villejuif, France. [Artaud,F, Severi,G] Institut Gustave Roussy, Villejuif, France. [Severi,G] Dipartimento di Statistica, Informatica e Applicazioni 'G. Parenti' (DISIA), University of Florence, Florence, Italy. [Trichopoulou,A, Karakatsani,A, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Panico,S] EPIC Centre of Naples, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy. [Masala,G] 1Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy. [Elias,SG, May,AM] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Borch,KB, Sandanger,TM, Skeie,G] Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway, Tromsø, Norway. [Sánchez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Sánchez,MJ, Huerta,JM, Gurrea,AB, Amiano,P] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Sala,N] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sala,N] Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Gurrea,AB] Navarra Public Health Institute, Pamplona, Spain. [Gurrea,AB] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Amiano,P] Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Donostia-San Sebastian, Spain. [Berntsson,J] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Drake,I] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [van Guelpen,B, Harlid,S] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Key,T] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., This work was supported by the German Research Foundation (DFG) (grant AL 1784/3-1), which funded the research position of Dr. Aleksandrova for organizing study conduct and analysis. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), Instituto de salud Carlos III PI13/00061 to Granada, PI13/ 01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and Catalonia (Catalan Institute of Oncology – ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (C864/A14136 to EPIC-Norfolk and C8221/A19170 to EPICOxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Open Access funding enabled and organized by Projekt DEAL.
Subjects: Male, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], lcsh:Medicine, Cancer prevention, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Calibration [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, Medicine, 030212 general & internal medicine, Prospective Studies, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], 10. No inequality, Prospective cohort study, 11 Medical and Health Sciences, Framingham Risk Score, Risk screening, Lifestyle behaviour, Risk prediction, Colorectal cancer, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], Female, Risk assessment, Colorectal Neoplasms, Research Article, Cohort study, Estils de vida, Waist, Lifestyles, Nutritional Status, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Estil de vida, Risk Assessment, Riesgo, Estilo de vida, 03 medical and health sciences, Càncer colorectal, General & Internal Medicine, Humans, Life Style, business.industry, lcsh:R, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk [Medical Subject Headings], Technology and Food and Beverages::Food and Beverages::Food::Vegetables [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Nomogram, Lifestyle, Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Check Tags::Female [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], business, Prevención de Enfermedades, Demography
Abstract: Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL
Published: 2021
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32. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author: Eva Ardanaz, Agnetha Linn Rostgaard-Hansen, Alessio Naccarati, Elisabete Weiderpass, Pekka Keski-Rahkonen, Rudolf Kaaks, Tilman Kühn, Anna Winkvist, Jośe Mariá Huerta, H. B. Bueno-De-Mesquita, Guri Skeie, Pietro Ferrari, Krasimira Aleksandrova, Gabriel Perlemuter, Augustin Scalbert, Olatz Mokoroa, Giovanna Tagliabue, Marc J. Gunter, Kim Overvad, José Ramón Quirós, Agneta Kiss, Marie-Christine Boutron-Ruault, Yahya Mahamat-Saleh, Talita Duarte-Salles, Nivonirina Robinot, Anne Tjønneland, Antonia Trichopoulou, Julie A. Schmidt, Christina C. Dahm, Roel Vermeulen, Rosario Tumino, Núria Sala, Joseph A. Rothwell, Sophia Harlid, Magdalena Stepien, Klas Sjöberg, Vivian Viallon, Neil Murphy, Anna Karakatsani, Salvatore Panico, Nicholas J. Wareham, María José Sánchez, Francesca Mancini, Domenico Palli, Mazda Jenab, Elio Riboli, Bodil Ohlsson, Kay-Tee Khaw, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National Du Cancer, INCa: 2014-1-RT-02-CIRC-1 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Cancer Research UK, CRUK: C570/A16491 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS National Research Council, NRC 6236 Hellenic Health Foundation, HHF Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, CIRC Associazione Italiana per la Ricerca sul Cancro, AIRC RD06/0020 Deutsche Krebshilfe World Cancer Research Fund, WCRF Cancerfonden Medical Research Council, MRC: MR/M012190/1, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA) (grant number 2014-1-RT-02-CIRC-1, PI: M. Jenab). The coordination of EPIC is financially supported by the European Commission (DG-SANCO), and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 for EPIC-Norfolk and C570/A16491 for EPIC-Oxford) and the Medical Research Council (1000143 for EPIC-Norfolk and MR/M012190/1 for EPIC-Oxford) (UK). The funding sources had no influence on the design of the study, the collection, analysis, and interpretation of data, the writing of the report, and or the decision to submit the paper for publication. Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, prospective observational cohort, Glycocholic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, Internal medicine, Biomarkers, Tumor, medicine, Humans, Metabolomics, Prospective Studies, Aged, Hepatitis, business.industry, Liver Neoplasms, Cancer, Feeding Behavior, hepatocellular carcinoma, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, untargeted metabolomics, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Female, business, Metabolic Networks and Pathways, Chromatography, Liquid, Cohort study
Abstract: International audience; Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
Published: 2020
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33. Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study

Author: Pietro Ferrari, Fulvio Ricceri, Christina C. Dahm, Kim Overvad, Sabina Sieri, Elisabete Weiderpass, Eleni Peppa, María José Sánchez, Leila Luján Barroso, Marta Solans Margalef, Matthias B. Schulze, Federico Canzian, Giovanna Masala, Florentin Spaeth, Dagfinn Aune, Roel Vermeulen, Tilman Kühn, Delphine Casabonne, Karin Jirstom, Anna Karakatsani, José María Huerta, Yahya Mahamat-Saleh, Paul Brennan, Cecilie Kyrø, Mats Jerkeman, Caroline Besson, Pilar Amiano Exezarreta, Virginia Menéndez, Elio Riboli, Julie A. Schmidt, Rosario Tumino, Sairah L.F. Chen, Marc J. Gunter, Eva Ardanaz, Antonia Trichopoulou, Alexandra Nieters, Marie-Christine Boutron-Ruault, Anne Tjønneland, Fatemeh Saberi Hosnijeh, Sabine Naudin, Salvatore Panico, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Centre Hospitalier de Versailles André Mignot (CHV), Direction Générale de la Compétitivité, de l’Industrie et des Services, DGCIS Food Standards Agency, FSA Cancer Research UK, CRUK: C864/A14136, C8221/A19170, C570/A16491 RD06/0020 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Université Claude Bernard Lyon 1, UCBL Wellcome Trust, WT Ligue Contre le Cancer 6236 German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Department of Health, Australian Government Ministry of Health and Social Solidarity, Greece Kræftens Bekæmpelse, DCS British Heart Foundation, BHF Instituto de Salud Carlos III, ISCIII National Research Council, NRC Mutuelle Générale de l'Education Nationale, MGEN Hellenic Health Foundation, HHF Stroke Association Institut National de la Santé et de la Recherche Médicale, Inserm Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, IARC Deutsche Krebshilfe Cancerfonden World Cancer Research Fund, WCRF Stavros Niarchos Foundation, SNF Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Medical Research Council, MRC: MR/M012190/1, MR/N003284/1, MC‐UU_12015/1, We thank Carine Biessy and Bertrand Hemon for their technical support and contribution to this work. We are also grateful to all the EPIC participants who have been part of the project and to the many other members of the study teams who have enabled this research. This work was supported by the Direction Générale de la Santé (French Ministry of Health, Grant GR‐IARC‐2003‐09‐12‐01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Health Research Fund, Regional Governments of Andalucýa, Asturias, Basque Country, Murcia (project 6236) and Navarra, Instituto de Salud Carlos III, Redes de Investigacion Cooperativa (RD06/0020, Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, and United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). This work was part of Sabine Naudin's PhD at Claude Bernard Lyon I University (France), funded by Région Auvergne Rhône‐Alpes, ADR 2016 (France).
Subjects: Male, Oncology, Cancer Research, Lymphoma, Body Mass Index, 0302 clinical medicine, Risk Factors, immune system diseases, hemic and lymphatic diseases, Prospective Studies, Prospective cohort study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, non-Hodgkin lymphoma, Smoking, Hazard ratio, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, 030220 oncology & carcinogenesis, Female, EPIC, healthy lifestyle index, Hodgkin lymphoma, prospective study, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Diet Surveys, 03 medical and health sciences, Internal medicine, REGRESSION, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Healthy Lifestyle, Exercise, Aged, Science & Technology, business.industry, Proportional hazards model, HODGKINS-LYMPHOMA, Feeding Behavior, medicine.disease, Confidence interval, Etiology, UPDATE, CIGARETTE-SMOKING, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Follow-Up Studies
Abstract: This is the peer reviewed version of the following article: Naudin, S., Margalef, M.S., Hosnijeh, F.S., Nieters, A., Kyrø, C. Tjønneland, A. ... Ferrari, P. (2020) Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer, 147(6):1649-1656, which has been published in final form at https://doi.org/10.1002/ijc.32977. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) were evaluated in a large‐scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow‐up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1‐standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1‐SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.
Published: 2020
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34. Degradation of proton depth dose distributions attributable to microstructures in lung-equivalent material

Author: Oelfke, Uwe [Department of Medical Physics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany and Department of Physics, The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP (United Kingdom)]
Published: 2015
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35. Segmentation-free empirical beam hardening correction for CT

Author: Kachelrieß, Marc [German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)]
Published: 2015
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36. Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations

Author: Katharina Nimptsch, Krasimira Aleksandrova, Veronika Fedirko, Mazda Jenab, Marc J. Gunter, Peter D. Siersema, Kana Wu, Verena Katzke, Rudolf Kaaks, Salvatore Panico, Domenico Palli, Anne M May, Sabina Sieri, Bas Bueno-de-Mesquita, Karina Standahl, Maria-Jose Sánchez, Aurora Perez-Cornago, Anja Olsen, Anne Tjønneland, Catalina Bonet Bonet, Christina C. Dahm, María-Dolores Chirlaque, Valentina Fiano, Rosario Tumino, Aurelio Barricarte Gurrea, Marie-Christine Boutron-Ruault, Florence Menegaux, Gianluca Severi, Bethany van Guelpen, Young-Ae Lee, Tobias Pischon, HAL UVSQ, Équipe, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Harvard T.H. Chan School of Public Health, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, University of Bremen, The University of Texas M.D. Anderson Cancer Center [Houston], Emory University [Atlanta, GA], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Radboud University Medical Center [Nijmegen], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, World Health Organization, WHO, Cancer Prevention and Research Institute of Texas, CPRIT: RR200056, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Consejería de Salud y Familias, Junta de Andalucía, NIHR Imperial Biomedical Research Centre, BRC, We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization., The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI https://doi.org/10.22025/2019.10.105.00004 ) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research., The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., and We acknowledge the use of data and biological samples from the EPIC-Asturias cohort, PI Jose-Ramon Quiros-Garcia and EPI-San Sebastian, PI Amiano Pilar. Veronika Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056).
Subjects: Cancer Research, Cancer och onkologi, Public Health, Global Health, Social Medicine and Epidemiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], C-Reactive Protein, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiovascular and Metabolic Diseases, Risk Factors, Cancer and Oncology, Genetics, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genetic Predisposition to Disease, Prospective Studies, Colorectal Neoplasms
Abstract: Background The role of elevated pre-diagnostic C-reactive protein (CRP) concentrations on mortality in individuals with colorectal cancer (CRC) remains unclear. Methods We investigated the association between pre-diagnostic high-sensitivity CRP concentrations and CRP genetic variation associated with circulating CRP and CRC-specific and all-cause mortality based on data from 1,235 individuals with CRC within the European Prospective Investigation into Cancer and Nutrition cohort using multivariable-adjusted Cox proportional hazards regression. Results During a median follow-up of 9.3 years, 455 CRC-specific deaths were recorded, out of 590 deaths from all causes. Pre-diagnostic CRP concentrations were not associated with CRC-specific (hazard ratio, HR highest versus lowest quintile 0.92, 95% confidence interval, CI 0.66, 1.28) or all-cause mortality (HR 0.91, 95% CI 0.68, 1.21). Genetic predisposition to higher CRP (weighted score based on alleles of four CRP SNPs associated with higher circulating CRP) was not significantly associated with CRC-specific mortality (HR per CRP-score unit 0.95, 95% CI 0.86, 1.05) or all-cause mortality (HR 0.98, 95% CI 0.90, 1.07). Among four investigated CRP genetic variants, only SNP rs1205 was significantly associated with CRC-specific (comparing the CT and CC genotypes with TT genotype, HR 0.54, 95% CI 0.35, 0.83 and HR 0.58, 95% CI 0.38, 0.88, respectively) and all-cause mortality (HR 0.58, 95% CI 0.40, 0.85 and 0.64, 95% CI 0.44, 0.92, respectively). Conclusions The results of this prospective cohort study do not support a role of pre-diagnostic CRP concentrations on mortality in individuals with CRC. The observed associations with rs1205 deserve further scientific attention.
Published: 2022
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37. Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition

Author: Marie Breeur, Pietro Ferrari, Laure Dossus, Mazda Jenab, Mattias Johansson, Sabina Rinaldi, Ruth C. Travis, Mathilde His, Tim J. Key, Julie A. Schmidt, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Joseph A. Rothwell, Nasser Laouali, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Fabian Eichelmann, Domenico Palli, Sara Grioni, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Bas Bueno-de-Mesquita, Karina Standahl Olsen, Torkjel Manning Sandanger, Therese Haugdahl Nøst, J. Ramón Quirós, Catalina Bonet, Miguel Rodríguez Barranco, María-Dolores Chirlaque, Eva Ardanaz, Malte Sandsveden, Jonas Manjer, Linda Vidman, Matilda Rentoft, David Muller, Kostas Tsilidis, Alicia K. Heath, Hector Keun, Jerzy Adamski, Pekka Keski-Rahkonen, Augustin Scalbert, Marc J. Gunter, Vivian Viallon, Cancer Research UK, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC: 2014/1183, C8221/A19170, Seventh Framework Programme, FP7: 2014/1193, 313010, C19335/A21351, National Research Council, NRC, World Cancer Research Fund International, WCRF, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, European Commission, EC, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Generalitat de Catalunya, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009-139, 2013/1002, 2014-1-RT-02-CIRC-1, 2015-166, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Consejería de Salud y Familias, Junta de Andalucía, NIHR Imperial Biomedical Research Centre, BRC, The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC)., This paper is dedicated to the memory our of colleague Dr. Bas Bueno-de-Mesquita. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). IDIBELL acknowledges support from the Generalitat de Catalunya through the CERCA Program. The breast cancer study was funded by the French National Cancer Institute (grant number 2015-166). The colorectal cancer studies were funded by World Cancer Research Fund (reference: 2013/1002, reference: 313010, reference: 2014/1193, INCa, grant numbers 2009-139 and 2014-1-RT-02-CIRC-1) and by internal funds of the IARC. For the participants in the prostate cancer study, sample retrieval and preparation, and assays of metabolites were supported by Cancer Research UK (C8221/A19170), and funding for grant 2014/1183 was obtained from the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme. Mathilde His’ work reported here was undertaken during the tenure of a postdoctoral fellowship awarded by the International Agency for Research on Cancer, financed by the Fondation ARC. The funders were not involved in designing the study, collecting, analysing, and interpreting results, or writing and submitting the manuscript for publication., and HAL UVSQ, Équipe
Subjects: Male, Carcinoma, Hepatocellular, Proline, Glutamine, Kidney, Risk Factors, General & Internal Medicine, Humans, Metabolomics, Histidine, Prospective Studies, Breast, Càncer, 11 Medical and Health Sciences, Colorectal, Cancer, Cancer och onkologi, Liver Neoplasms, Prostate, Lysophosphatidylcholines, General Medicine, Sphingomyelins, Metabolòmica, Liver, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Cancer and Oncology, Carcinoma, Hepatocellular/diagnosis, Phosphatidylcholines, Epic, Endometrial, Lasso, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, EPIC
Abstract: Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. Results Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. Conclusions These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
Published: 2022
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38. Gain-of-Function Mutations in RPA1 Cause a Syndrome with Short Telomeres and Somatic Genetic Rescue

Author: Masayoshi Honda, Melchior Lauten, Marcus B. Valentine, Patrick Revy, Stéphane Coulon, Richa Sharma, Charnise Goodings, Caroline Kannengiesser, Fabian Beier, Melanie Boerries, Shondra M. Pruett-Miller, Sophie L Granger, Miriam Erlacher, Maria Spies, Axel Künstner, Megan A. Cooper, Jill A. Rosenfeld, Vincent Géli, Carole Saintomé, Victor B Pastor, Charlotte M. Niemeyer, Dmitri Churikov, Marcin W. Wlodarski, Sophia Polychronopoulou, Hauke Busch, Ti-Cheng Chang, Sandrine Hirschi, Louis Sanchez, Charikleia Kelaidi, Sushree S. Sahoo, Marc S. Wold, Alfonso G Fernandez, Sarah K. Nicholas, Indian Institute of Technology Delhi (IIT Delhi), Uppsala University, Freiburg Institute for Advanced Studies-LifeNet, Albert-Ludwigs-Universität Freiburg, St Jude Children's Research Hospital, University of Iowa [Iowa City], Sorbonne Université (SU), Universität zu Lübeck = University of Lübeck [Lübeck], Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Strasbourg, Université de Strasbourg (UNISTRA), German Cancer Consortium [Heidelberg] (DKTK), University Hospital Schleswig-Holstein-Campus Luebeck, 'Aghia Sophia' Children's Hospital, University of Freiburg [Freiburg], Washington University in Saint Louis (WUSTL), Baylor College of Medicine (BCM), Baylor University, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Muséum national d'Histoire naturelle (MNHN), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Washington University School of Medicine in St. Louis, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Sorbonne Université - UFR Sciences de la vie (UFR 927 ), Universität zu Lübeck [Lübeck], RWTH Aachen University, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Adult, Male, Heterozygote, Adolescent, Somatic cell, [SDV]Life Sciences [q-bio], Immunology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, medicine.disease_cause, Biochemistry, Germline, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Replication Protein A, medicine, Missense mutation, Humans, Child, Gene, Telomere Shortening, 030304 developmental biology, Genetics, 0303 health sciences, Mutation, Infant, Newborn, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Differentiation, Cell Biology, Hematology, DNA-binding domain, Bone Marrow Failure Disorders, Middle Aged, Telomere, 3. Good health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Gain of Function Mutation, Myelodysplastic Syndromes, Female, Blood Commentary, Stem cell, 030215 immunology
Abstract: Human telomere biology disorders (TBD)/short telomere syndromes (STS) are heterogeneous disorders caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify 3 germline heterozygous missense variants in the RPA1 gene in 4 unrelated probands presenting with short telomeres and varying clinical features of TBD/STS, including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, or skin manifestations. All variants cluster to DNA-binding domain A of RPA1 protein. RPA1 is a single-strand DNA-binding protein required for DNA replication and repair and involved in telomere maintenance. We showed that RPA1E240K and RPA1V227A proteins exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function, whereas RPA1T270A has binding properties similar to wild-type protein. To study the mutational effect in a cellular system, CRISPR/Cas9 was used to knock-in the RPA1E240K mutation into healthy inducible pluripotent stem cells. This resulted in severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in patients with RPA1E240K, we discovered somatic genetic rescue in hematopoietic cells due to an acquired truncating cis RPA1 mutation or a uniparental isodisomy 17p with loss of mutant allele, coinciding with stabilized blood counts. Using single-cell sequencing, the 2 somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD/STS.
Published: 2021
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39. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors

Author: Karger, C. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany)]
Published: 2015
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40. Robust primary modulation-based scatter estimation for cone-beam CT

Author: Kachelrieß, Marc [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120 (Germany)]
Published: 2015
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41. Alpha image reconstruction (AIR): A new iterative CT image reconstruction approach using voxel-wise alpha blending

Author: Kachelrieß, Marc [Institute of Medical Physics, Friedrich-Alexander University (FAU), Erlangen 91052, Germany and Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany)]
Published: 2014
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42. SU-E-T-215: Interactive Dose Shaping: Proof of Concept Study for Six Prostate Patients

Author: Sterzing, F [German Cancer Research Center (DKFZ), Heidelberg (Germany)]
Published: 2014
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43. SU-E-J-273: Simulation of the Radiation Response of Hypoxic Tumors

Author: Karger, C [German Cancer Research Center (DKFZ), Heidelberg (Germany)]
Published: 2014
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44. Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

Author: Kachelrieß, Marc [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany and Institute of Medical Physics, University of Erlangen–Nürnberg, 91052 Erlangen (Germany)]
Published: 2014
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45. Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

Author: Karger, Christian [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)]
Published: 2014
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46. Prior-based artifact correction (PBAC) in computed tomography

Author: Kachelrieß, Marc [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany and Institute of Medical Physics, Friedrich–Alexander–University (FAU) of Erlangen–Nürnberg, Henkestraße 91, 91052 Erlangen (Germany)]
Published: 2014
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47. Effects of ray profile modeling on resolution recovery in clinical CT

Author: Kachelrieß, Marc [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany and Institute of Medical Physics, Friedrich–Alexander University (FAU), Erlangen, Bavaria 91052 (Germany)]
Published: 2014
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48. Pre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma

Author: Heinz Freisling, Susana Merino, Aurelio Barricarte, Augustin Scalbert, Domenico Palli, Eleni Peppa, Hanna Nyström, Klas Sjöberg, Magdalena Stepien, Antonia Trichopoulou, Aurora Perez-Cornago, Marina Lopez-Nogueroles, Gianluca Severi, Carlotta Sacerdote, Dragos Ciocan, Tilman Kühn, Elisabete Weiderpass, Cosmin Sebastian Voican, Manuela M. Bergmann, Gabriel Perlemuter, Eugene Jansen, Rudolf Kaaks, Michael F. Leitzmann, Julie A. Schmidt, Catherine Dong, Anna Karakatsani, María José Sánchez, Rosario Tumino, Bodil Ohlsson, H. Bas Bueno-de-Mesquita, Marc J. Gunter, Raul Zamora Ros, Guri Skeie, José Mª Huerta, Heiner Boeing, Agustín Lahoz, Vittorio Krogh, Pilar Amiano, Francesca Mancini, Anne Tjønneland, Marie-Christine Boutron-Ruault, Salvatore Panico, Mazda Jenab, Sofia Christakoudi, Vivian Viallon, Renée T. Fortner, Mårten Werner, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: 1000143, MR/M012190/1, Cancer Research UK, CRUK: 14136, C8221/A29017, World Cancer Research Fund, WCRF, University of Cambridge, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Deutsche Krebshilfe, Institut National Du Cancer, INCa: 2009‐139, 2014‐1‐RT‐02‐CIRC‐1, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, This work was supported in part by the French National Cancer Institute (L'Institut National du Cancer, INCa, grant numbers 2009‐139 and 2014‐1‐RT‐02‐CIRC‐1, PI: M. Jenab) and by internal funds of the IARC. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam‐Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C8221/A29017 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford) (United Kingdom). The funding sources had no influence on the design of the study, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication. Funding information, and We would like to acknowledge Dr Krasimira Aleksandrova for input on the present manuscript, along with the National Institute for Public Health and the Environment (Bilthoven, The Netherlands), the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands, Department of Public Health Aarhus University (Aarhus, Denmark), University of Cambridge (Cambridge, United Kingdom), for their contributions and ongoing support to the EPIC Study.
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, obesity, Carcinoma, Hepatocellular, medicine.drug_class, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Bile Acids and Salts, Cohort Studies, chemistry.chemical_compound, Internal medicine, medicine, Biomarkers, Tumor, Choline, Humans, Prospective cohort study, Carcinogen, Aged, Cancer prevention, Bile acid, cancer prevention, business.industry, Confounding, Liver Neoplasms, bile acid metabolism, biomarkers, hepatocellular carcinoma, Middle Aged, medicine.disease, Obesity, Oncology, chemistry, Hepatocellular carcinoma, Case-Control Studies, Female, business
Abstract: This is the peer reviewed version of the following article: Stepien et.al (2021). Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.33885. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.
Published: 2021
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49. Transforming Growth Factor-beta signaling in αβ thymocytes promotes negative selection

Author: Arnauld Sergé, Mark J. McCarron, Saïdi M. Soudja, Magali Irla, Julien C. Marie, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Développement Cancer et Thérapies Ciblées [Lyon] (LabEx DEVweCAN), Université de Lyon, Genentech, Inc. [San Francisco], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre for Cellular and Molecular Biology of Inflammation, King‘s College London, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), and German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)
Subjects: 0301 basic medicine, Central tolerance, T cell, Cellular differentiation, Science, T cells, General Physics and Astronomy, Autoimmunity, Bone Marrow Cells, Biology, CXCR3, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Negative selection, 0302 clinical medicine, Transforming Growth Factor beta, medicine, Animals, lcsh:Science, Mice, Knockout, Multidisciplinary, Thymocytes, RANK Ligand, Cell Differentiation, Epithelial Cells, General Chemistry, T lymphocyte, Transforming growth factor beta, Cell biology, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, Signal transduction, 030215 immunology, Transforming growth factor, Signal Transduction
Abstract: In the thymus, the T lymphocyte repertoire is purged of a substantial portion of highly self-reactive cells. This negative selection process relies on the strength of TCR-signaling in response to self-peptide-MHC complexes, both in the cortex and medulla regions. However, whether cytokine-signaling contributes to negative selection remains unclear. Here, we report that, in the absence of Transforming Growth Factor beta (TGF-β) signaling in thymocytes, negative selection is significantly impaired. Highly autoreactive thymocytes first escape cortical negative selection and acquire a Th1-like-phenotype. They express high levels of CXCR3, aberrantly accumulate at the cortico-medullary junction and subsequently fail to sustain AIRE expression in the medulla, escaping medullary negative selection. Highly autoreactive thymocytes undergo an atypical maturation program, substantially accumulate in the periphery and induce multiple organ-autoimmune-lesions. Thus, these findings reveal TGF-β in thymocytes as crucial for negative selection with implications for understanding T cell self-tolerance mechanisms., TGFβ is critical for limiting autoreactive responses of peripheral T cells. Here, the authors show that TGFβ signaling in thymocytes mediates elimination of self-reactive T cells and promotes the expression of self-antigens by medullary thymic epithelial cells.
Published: 2019
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50. Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models

Author: Raymond Pieters, Klaus Gjervig Jensen, Philip G. Hewitt, Jan Snoeys, Bob van de Water, B. Kevin Park, Ursula Klingmüller, André Guillouzo, Ian M. Copple, Dominic P. Williams, Michael J. Liguori, Cerys A. Lovatt, Paul Morgan, Satu Juhila, Eric A.G. Blomme, Magnus Ingelman-Sundberg, Dean J. Naisbitt, Gilles Labbe, Amy E. Chadwick, Christopher E. Goldring, Helga H.J. Gerets, Richard J. Weaver, Jonchère, Laurent, Mechanism-Based Integrated Systems for the Prediction of Drug-Induced Liver Injury - MIP-DILI - - EC:FP7:SP1-JTI2012-02-01 - 2017-01-31 - 115336 - VALID, University of Liverpool, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Merck Research Laboratories, Karolinska Institutet [Stockholm], Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), SANOFI Recherche, Abbvie Inc. [North Chicago], GlaxoSmithKline, Glaxo Smith Kline, AstraZeneca, University Medical Center [Utrecht], Janssen Research & Development, Leiden University, Institut de Recherches Internationales Servier [Suresnes] (IRIS), UCB BioPharma [Braine l’Alleud, Belgium], This work was supported by the European Community (Contract MIP-DILI-115336) under the Innovative Medicines Initiative Joint Undertaking, a contribution from the European Union's Seventh Framework Programme (FP7/20072013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies (http://www.imi.europa.eu/) and by the German Ministry of Education and Research (BMBF) within ‘Multi-Scale Modeling of Drug-Induced Liver Injury’ (MS_DILI, 031L0074A)., European Project: 115336,EC:FP7:SP1-JTI,IMI-JU-03-2010,MIP-DILI(2012), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Universiteit Leiden
Subjects: 0301 basic medicine, Drug, Drug-Related Side Effects and Adverse Reactions, [SDV]Life Sciences [q-bio], media_common.quotation_subject, In vitro model, 03 medical and health sciences, Preclinical research, 0302 clinical medicine, Predictive Value of Tests, Drug Discovery, Animals, Humans, Medicine, media_common, Pharmacology, Adverse effects, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], Disease Models, Animal, 030104 developmental biology, Risk analysis (engineering), Software deployment, Preclinical testing, 030220 oncology & carcinogenesis, Chemical and Drug Induced Liver Injury, business
Abstract: International audience; Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current preclinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction. This Perspective defines the current status of available models and the mechanistic understanding of DILI, and proposes our vision of a roadmap for the development of predictive preclinical models of human DILI.
Published: 2019
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