Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.
We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1-16. ©2016 AACR.
Cancer discovery. 2016 Jul 17 [Epub ahead of print]
Siddhartha P Kar, Jonathan Beesley, Ali Amin Al Olama, Kyriaki Michailidou, Jonathan Tyrer, ZSofia Kote-Jarai, Kate Lawrenson, Sara Lindstrom, Susan J Ramus, Deborah J Thompson, ABCTB Investigators , Adam S Kibel, Agnieszka Dansonka-Mieszkowska, Agnieszka Michael, Aida K Dieffenbach, Aleksandra Gentry-Maharaj, Alice S Whittemore, Alicja Wolk, Alvaro Monteiro, Ana Peixoto, Andrzej Kierzek, Angela Cox, Anja Rudolph, Anna Gonzalez-Neira, Anna H Wu, Annika Lindblom, Anthony Swerdlow, AOCS Study Group & Australian Cancer Study (Ovarian Cancer) , APCB BioResource , Argyrios Ziogas, Arif B Ekici, Barbara Burwinkel, Beth Y Karlan, Børge G Nordestgaard, Carl Blomqvist, Catherine Phelan, Catriona McLean, Celeste Leigh Pearce, Celine Vachon, Cezary Cybulski, Chavdar Slavov, Christa Stegmaier, Christiane Maier, Christine B Ambrosone, Claus K Høgdall, Craig C Teerlink, Daehee Kang, Daniel C Tessier, Daniel J Schaid, Daniel O Stram, Daniel W Cramer, David E Neal, Diana Eccles, Dieter Flesch-Janys, Digna R Velez Edwards, Dominika Wokozorczyk, Douglas A Levine, Drakoulis Yannoukakos, Elinor J Sawyer, Elisa V Bandera, Elizabeth M Poole, Ellen L Goode, Elza Khusnutdinova, Estrid Høgdall, Fengju Song, Fiona Bruinsma, Florian Heitz, Francesmary Modugno, Freddie C Hamdy, Fredrik Wiklund, Graham G Giles, Håkan Olsson, Hans Wildiers, Hans-Ulrich Ulmer, Hardev Pandha, Harvey A Risch, Hatef Darabi, Helga B Salvesen, Heli Nevanlinna, Henrik Gronberg, Hermann Brenner, Hiltrud Brauch, Hoda Anton-Culver, Honglin Song, Hui-Yi Lim, Iain McNeish, Ian Campbell, Ignace Vergote, Jacek Gronwald, Jan Lubiński, Janet L Stanford, Javier Benítez, Jennifer A Doherty, Jennifer B Permuth, Jenny Chang-Claude, Jenny L Donovan, Joe Dennis, Joellen M Schildkraut, Johanna Schleutker, John L Hopper, Jolanta Kupryjanczyk, Jong Y Park, Jonine Figueroa, Judith A Clements, Julia A Knight, Julian Peto, Julie M Cunningham, Julio Pow-Sang, Jyotsna Batra, Kamila Czene, Karen H Lu, Kathleen Herkommer, Kay-Tee Khaw, kConFab Investigators , Keitaro Matsuo, Kenneth Muir, Kenneth Offitt, Kexin Chen, Kirsten B Moysich, Kristiina Aittomäki, Kunle Odunsi, Lambertus A Kiemeney, Leon F A G Massuger, Liesel M Fitzgerald, Linda S Cook, Lisa Cannon-Albright, Maartje J Hooning, Malcolm C Pike, Manjeet K Bolla, Manuel Luedeke, Manuel R Teixeira, Marc T Goodman, Marjanka K Schmidt, Marjorie Riggan, Markus Aly, Mary Anne Rossing, Matthias W Beckmann, Matthieu Moisse, Maureen Sanderson, Melissa C Southey, Michael Jones, Michael Lush, Michelle A T Hildebrandt, Ming-Feng Hou, Minouk J Schoemaker, Montserrat Garcia-Closas, Natalia Bogdanova, Nazneen Rahman, NBCS Investigators , Nhu D Le, Nick Orr, Nicolas Wentzensen, Nora Pashayan, Paolo Peterlongo, Pascal Guénel, Paul Brennan, Paula Paulo, Penelope M Webb, Per Broberg, Peter A Fasching, Peter Devilee, Qin Wang, Qiuyin Cai, Qiyuan Li, Radka Kaneva, Ralf Butzow, Reidun Kristin Kopperud, Rita K Schmutzler, Robert A Stephenson, Robert J MacInnis, Robert N Hoover, Robert Winqvist, Roberta Ness, Roger L Milne, Ruth C Travis, Sara Benlloch, Sara H Olson, Shannon K McDonnell, Shelley S Tworoger, Sofia Maia, Sonja Berndt, Soo Chin Lee, Soo-Hwang Teo, Stephen N Thibodeau, Stig E Bojesen, Susan M Gapstur, Susanne Krüger Kjær, Tanja Pejovic, Teuvo L J Tammela, GENICA Network , PRACTICAL consortium , Thilo Dörk, Thomas Brüning, Tiina Wahlfors, Tim J Key, Todd L Edwards, Usha Menon, Ute Hamann, Vanio Mitev, Veli-Matti Kosma, Veronica Wendy Setiawan, Vessela Kristensen, Volker Arndt, Walther Vogel, Wei Zheng, Weiva Sieh, William J Blot, Wojciech Kluzniak, Xiao-Ou Shu, Yu-Tang Gao, Fredrick Schumacher, Matthew L Freedman, Andrew Berchuck, Alison M Dunning, Jacques Simard, Christopher A Haiman, Amanda Spurdle, Thomas A Sellers, David J Hunter, Brian E Henderson, Peter Kraft, Stephen J Chanock, Fergus J Couch, Per Hall, Simon A Gayther, Douglas F Easton, Georgia Chenevix-Trench, Rosalind Eeles, Paul D P Pharoah, Diether Lambrechts
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. ., Department of Genetics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., The Institute of Cancer Research, Sutton, UK., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Division of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts., Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland., The University of Surrey, Guildford, UK., Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Women's Cancer, Institute for Women's Health, University College London, London, UK., Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California., Karolinska Institutet, Department of Environmental Medicine, Division of Nutritional Epidemiology, Stockholm, Sweden., Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida., Department of Genetics, Portuguese Oncology Institute, Porto, Portugal., The University of Surrey, Guildford, UK., Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK., Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) and Spanish National Genotyping Center (CEGEN), Madrid, Spain., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK., Department of Epidemiology, UCI Center for Cancer Genetics Research and Prevention, School of Medicine, University of California, Irvine, Irvine, California., University Hospital Erlangen, Institute of Human Genetics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany., Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California., Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark., Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida., Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria, Australia., Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan., Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota., International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Department of Urology, Alexandrovska University Hospital, Medical University, Sofia, Bulgaria., Saarland Cancer Registry, Saarbrücken, Germany., Department of Urology, University Hospital Ulm, Ulm, Germany., Roswell Park Cancer Institute, Buffalo, New York., The Juliane Marie Centre, Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah., Cancer Research Institute, Seoul National University, Seoul, Korea. Departments of Preventive Medicine and Surgery, Seoul National University College of Medicine, Seoul, Korea., McGill University and Génome Québec Innovation Centre, Montréal, Canada., Mayo Clinic, Rochester, Minnesota., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts., Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK., Faculty of Medicine, University of Southampton, Southampton, UK., University Medical Center Hamburg-Eppendorf, Institute of Occupational Medicine and Maritime Medicine and Institute for Medical Biometrics and Epidemiology, Hamburg, Germany., Vanderbilt Epidemiology Center, Vanderbilt Genetics Institute, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee., International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Molecular Diagnostics Laboratory, NCSR Demokritos, Agia Paraskevi, Athens, Greece., Research Oncology, Guy's Hospital, King's College London, London, UK., Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, The State University of New Jersey, New Brunswick, New Jersey., Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts., Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota., Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russia. Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia., Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark., Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China., Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia., Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany. Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany., Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania. Women's Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania., Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia., Departments of Cancer Epidemiology and Oncology, University Hospital, Lund, Sweden., Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium., Frauenklinik der Stadtklinik Baden-Baden, Baden-Baden, Germany., The University of Surrey, Guildford, UK., Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway. Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway., Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany., German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. University of Tübingen, Tübingen, Germany., Department of Epidemiology, UCI Center for Cancer Genetics Research and Prevention, School of Medicine, University of California, Irvine, Irvine, California., Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Biostatistics Program, Moffitt Cancer Center, Tampa, Florida., Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK., Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria, Australia. Department of Pathology, University of Melbourne, Parkville, Victoria, Australia., Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium., International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, University of Washington, Seattle, Washington., Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) and Spanish National Genotyping Center (CEGEN), Madrid, Spain., Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire., Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida., Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., School of Social and Community Medicine, University of Bristol, Bristol, UK., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina. Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina., Department of Medical Biochemistry and Genetics Institute of Biomedicine, University of Turku, Turku, Finland. BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland., Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia., Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland., Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida., Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Australian Prostate Cancer Research Centre, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia., Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada. Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada., Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK., Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida., Australian Prostate Cancer Research Centre, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Department of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany., Clinical Gerontology Unit, University of Cambridge, Cambridge, UK., Department of Preventive Medicine, Kyushu University Faculty of Medical Science, Nagoya, Aichi, Japan., Institute of Population Health, University of Manchester, Manchester, UK. Warwick Medical School, University of Warwick, Coventry, UK., Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York. Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China., Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York., Department of Clinical Genetics, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York., Radboud University Medical Centre, Radbond Institute for Health Sciences, Nijmegen, the Netherlands., Department of Gynaecology, Radboud University Medical Center, Nijmegen, the Netherlands., Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia., Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico., George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah., Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Department of Urology, University Hospital Ulm, Ulm, Germany., Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal., Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, and Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California., Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands., Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Department of Clinical Sciences, Danderyds Hospital, Stockholm, Sweden., Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, University of Washington, Seattle, Washington., Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., VIB Vesalius Research Center, KU Leuven, Leuven, Belgium., Department of Family and Community Medicine, Meharry Medical College, Nashville, Tennessee., Department of Pathology, University of Melbourne, Parkville, Victoria, Australia., Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Cancer Center and Department of Surgery, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany., Section of Cancer Genetics, The Institute of Cancer Research, London, UK., Cancer Control Research, British Columbia Cancer Agency, Vancouver, Canada., Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK., Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. Department of Applied Health Research, University College London, London, UK., IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy., Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France. University Paris-Sud, Villejuif, France., International Agency for Research on Cancer, Lyon, France., Department of Genetics, Portuguese Oncology Institute, Porto, Portugal., Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Department of Cancer Epidemiology, University Hospital, Lund, Sweden., Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Departments of Human Genetics and of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee., Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts. Medical College of Xiamen University, Xiamen, China., Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, Bulgaria., Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Department of Pathology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway. Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway., Center for Integrated Oncology (CIO) and Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah., Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia., Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Laboratory of Cancer Genetics and Tumor Biology, Cancer Research and Translational Medicine, Biocenter Oulu, University of Oulu, and Northern Finland Laboratory Centre, Oulu, Finland., The University of Texas School of Public Health, Houston, Texas., Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia., Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York., Mayo Clinic, Rochester, Minnesota., Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts., Department of Genetics, Portuguese Oncology Institute, Porto, Portugal., Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Department of Hematology-Oncology, National University Health System, Singapore. Cancer Science Institute of Singapore, National University of Singapore, Singapore., Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia. University of Malaya Cancer Research Institute, University Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia., Mayo Clinic, Rochester, Minnesota., Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark., Epidemiology Research Program, American Cancer Society, Atlanta, Georgia., Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Department of Obstetrics and Gynecology, and Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon., Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland., Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany., Department of Medical Biochemistry and Genetics Institute of Biomedicine, University of Turku, Turku, Finland., Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee., Women's Cancer, Institute for Women's Health, University College London, London, UK., Frauenklinik der Stadtklinik Baden-Baden, Baden-Baden, Germany., Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, Bulgaria., Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Department of Pathology, Kuopio University Hospital, Kuopio, Finland., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway., Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Institute of Human Genetics, University Hospital Ulm, Ulm, Germany., Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee., Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California., Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee., International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee., Shanghai Cancer Institute, Shanghai, P.R. China., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. The Eli and Edythe L. Broad Institute, Cambridge, Massachusetts., Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina., Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Molecular Cancer Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida., Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts., Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Department of Genetics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., The Institute of Cancer Research, Sutton, UK. Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK., Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., VIB Vesalius Research Center, KU Leuven, Leuven, Belgium.