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

Kar SP 1 , Beesley J 2 , Amin Al Olama A 3 , Michailidou K 3 , Tyrer J 4 , Kote-Jarai Z 5 Show all authors , Lawrenson K 6 , Lindstrom S 7 , Ramus SJ 6 , Thompson DJ 3 , ABCTB Investigators , Kibel AS 8 , Dansonka-Mieszkowska A 9 , Michael A 10 , Dieffenbach AK 11 , Gentry-Maharaj A 12 , Whittemore AS 13 , Wolk A 14 , Monteiro A 15 , Peixoto A 16 , Kierzek A 10 , Cox A 17 , Rudolph A 18 , Gonzalez-Neira A 19 , Wu AH 6 , Lindblom A 20 , Swerdlow A 21 , AOCS Study Group & Australian Cancer Study (Ovarian Cancer) , APCB BioResource , Ziogas A 22 , Ekici AB 23 , Burwinkel B 24 , Karlan BY 25 , Nordestgaard BG 26 , Blomqvist C 27 , Phelan C 15 , McLean C 28 , Pearce CL 29 , Vachon C 30 , Cybulski C 31 , Slavov C 32 , Stegmaier C 33 , Maier C 34 , Ambrosone CB 35 , Høgdall CK 36 , Teerlink CC 37 , Kang D 38 , Tessier DC 39 , Schaid DJ 40 , Stram DO 6 , Cramer DW 41 , Neal DE 42 , Eccles D 43 , Flesch-Janys D 44 , Edwards DR 45 , Wokozorczyk D 31 , Levine DA 46 , Yannoukakos D 47 , Sawyer EJ 48 , Bandera EV 49 , Poole EM 50 , Goode EL 30 , Khusnutdinova E 51 , Høgdall E 52 , Song F 53 , Bruinsma F 54 , Heitz F 55 , Modugno F 56 , Hamdy FC 57 , Wiklund F 58 , Giles GG 59 , Olsson H 60 , Wildiers H 61 , Ulmer HU 62 , Pandha H 10 , Risch HA 63 , Darabi H 58 , Salvesen HB 64 , Nevanlinna H 65 , Gronberg H 58 , Brenner H 66 , Brauch H 67 , Anton-Culver H 22 , Song H 4 , Lim HY 68 , McNeish I 69 , Campbell I 70 , Vergote I 71 , Gronwald J 31 , Lubiński J 31 , Stanford JL 72 , Benítez J 19 , Doherty JA 73 , Permuth JB 15 , Chang-Claude J 18 , Donovan JL 74 , Dennis J 3 , Schildkraut JM 75 , Schleutker J 76 , Hopper JL 77 , Kupryjanczyk J 9 , Park JY 15 , Figueroa J 78 , Clements JA 79 , Knight JA 80 , Peto J 81 , Cunningham JM 82 , Pow-Sang J 15 , Batra J 79 , Czene K 58 , Lu KH 83 , Herkommer K 84 , Khaw KT 85 , kConFab Investigators , Matsuo K 86 , Muir K 87 , Offitt K 88 , Chen K 53 , Moysich KB 89 , Aittomäki K 90 , Odunsi K 91 , Kiemeney LA 92 , Massuger LF 93 , Fitzgerald LM 54 , Cook LS 94 , Cannon-Albright L 95 , Hooning MJ 96 , Pike MC 97 , Bolla MK 3 , Luedeke M 34 , Teixeira MR 98 , Goodman MT 99 , Schmidt MK 100 , Riggan M 101 , Aly M 102 , Rossing MA 72 , Beckmann MW 103 , Moisse M 104 , Sanderson M 105 , Southey MC 106 , Jones M 107 , Lush M 3 , Hildebrandt MA 108 , Hou MF 109 , Schoemaker MJ 107 , Garcia-Closas M 110 , Bogdanova N 111 , Rahman N 112 , NBCS Investigators , Le ND 113 , Orr N 114 , Wentzensen N 78 , Pashayan N 115 , Peterlongo P 116 , Guénel P 117 , Brennan P 118 , Paulo P 16 , Webb PM 119 , Broberg P 120 , Fasching PA 103 , Devilee P 121 , Wang Q 3 , Cai Q 122 , Li Q 123 , Kaneva R 124 , Butzow R 125 , Kopperud RK 64 , Schmutzler RK 126 , Stephenson RA 127 , MacInnis RJ 128 , Hoover RN 78 , Winqvist R 129 , Ness R 130 , Milne RL 128 , Travis RC 131 , Benlloch S 3 , Olson SH 97 , McDonnell SK 40 , Tworoger SS 50 , Maia S 16 , Berndt S 78 , Lee SC 132 , Teo SH 133 , Thibodeau SN 40 , Bojesen SE 134 , Gapstur SM 135 , Kjær SK 136 , Pejovic T 137 , Tammela TL 138 , GENICA Network , PRACTICAL consortium , Dörk T 139 , Brüning T 140 , Wahlfors T 141 , Key TJ 131 , Edwards TL 142 , Menon U 12 , Hamann U 62 , Mitev V 124 , Kosma VM 143 , Setiawan VW 6 , Kristensen V 144 , Arndt V 145 , Vogel W 146 , Zheng W 122 , Sieh W 13 , Blot WJ 147 , Kluzniak W 31 , Shu XO 122 , Gao YT 148 , Schumacher F 6 , Freedman ML 149 , Berchuck A 101 , Dunning AM 4 , Simard J 150 , Haiman CA 6 , Spurdle A 151 , Sellers TA 15 , Hunter DJ 7 , Henderson BE 6 , Kraft P 7 , Chanock SJ 78 , Couch FJ 82 , Hall P 58 , Gayther SA 6 , Easton DF 152 , Chenevix-Trench G 2 , Eeles R 153 , Pharoah PD 152 , Lambrechts D 104

Affiliations 

  • 1 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. sk718@medschl.cam.ac.uk
  • 2 Department of Genetics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  • 3 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 4 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
  • 5 The Institute of Cancer Research, Sutton, UK
  • 6 Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California
  • 7 Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts
  • 8 Division of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 9 Department of Pathology and Laboratory Diagnostics, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
  • 10 The University of Surrey, Guildford, UK
  • 11 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
  • 12 Women's Cancer, Institute for Women's Health, University College London, London, UK
  • 13 Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, California
  • 14 Karolinska Institutet, Department of Environmental Medicine, Division of Nutritional Epidemiology, Stockholm, Sweden
  • 15 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida
  • 16 Department of Genetics, Portuguese Oncology Institute, Porto, Portugal
  • 17 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK
  • 18 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 19 Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) and Spanish National Genotyping Center (CEGEN), Madrid, Spain
  • 20 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  • 21 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK
  • 22 Department of Epidemiology, UCI Center for Cancer Genetics Research and Prevention, School of Medicine, University of California, Irvine, Irvine, California
  • 23 University Hospital Erlangen, Institute of Human Genetics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
  • 24 Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 25 Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
  • 26 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 27 Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
  • 28 Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria, Australia
  • 29 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan
  • 30 Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota
  • 31 International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 32 Department of Urology, Alexandrovska University Hospital, Medical University, Sofia, Bulgaria
  • 33 Saarland Cancer Registry, Saarbrücken, Germany
  • 34 Department of Urology, University Hospital Ulm, Ulm, Germany
  • 35 Roswell Park Cancer Institute, Buffalo, New York
  • 36 The Juliane Marie Centre, Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 37 Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
  • 38 Cancer Research Institute, Seoul National University, Seoul, Korea. Departments of Preventive Medicine and Surgery, Seoul National University College of Medicine, Seoul, Korea
  • 39 McGill University and Génome Québec Innovation Centre, Montréal, Canada
  • 40 Mayo Clinic, Rochester, Minnesota
  • 41 Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts
  • 42 Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK
  • 43 Faculty of Medicine, University of Southampton, Southampton, UK
  • 44 University Medical Center Hamburg-Eppendorf, Institute of Occupational Medicine and Maritime Medicine and Institute for Medical Biometrics and Epidemiology, Hamburg, Germany
  • 45 Vanderbilt Epidemiology Center, Vanderbilt Genetics Institute, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee
  • 46 Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
  • 47 Molecular Diagnostics Laboratory, NCSR Demokritos, Agia Paraskevi, Athens, Greece
  • 48 Research Oncology, Guy's Hospital, King's College London, London, UK
  • 49 Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, The State University of New Jersey, New Brunswick, New Jersey
  • 50 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
  • 51 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
  • 52 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
  • 53 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
  • 54 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
  • 55 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
  • 56 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
  • 57 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK
  • 58 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
  • 59 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
  • 60 Departments of Cancer Epidemiology and Oncology, University Hospital, Lund, Sweden
  • 61 Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium
  • 62 Frauenklinik der Stadtklinik Baden-Baden, Baden-Baden, Germany
  • 63 Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut
  • 64 Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway. Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway
  • 65 Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
  • 66 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
  • 67 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
  • 68 Biostatistics Program, Moffitt Cancer Center, Tampa, Florida
  • 69 Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK
  • 70 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
  • 71 Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium
  • 72 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, University of Washington, Seattle, Washington
  • 73 Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
  • 74 School of Social and Community Medicine, University of Bristol, Bristol, UK
  • 75 Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina. Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina
  • 76 Department of Medical Biochemistry and Genetics Institute of Biomedicine, University of Turku, Turku, Finland. BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland
  • 77 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
  • 78 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 79 Australian Prostate Cancer Research Centre, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia
  • 80 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
  • 81 Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  • 82 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
  • 83 Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
  • 84 Department of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany
  • 85 Clinical Gerontology Unit, University of Cambridge, Cambridge, UK
  • 86 Department of Preventive Medicine, Kyushu University Faculty of Medical Science, Nagoya, Aichi, Japan
  • 87 Institute of Population Health, University of Manchester, Manchester, UK. Warwick Medical School, University of Warwick, Coventry, UK
  • 88 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
  • 89 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York
  • 90 Department of Clinical Genetics, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
  • 91 Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York
  • 92 Radboud University Medical Centre, Radbond Institute for Health Sciences, Nijmegen, the Netherlands
  • 93 Department of Gynaecology, Radboud University Medical Center, Nijmegen, the Netherlands
  • 94 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico
  • 95 George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
  • 96 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
  • 97 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
  • 98 Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal
  • 99 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
  • 100 Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
  • 101 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina
  • 102 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Department of Clinical Sciences, Danderyds Hospital, Stockholm, Sweden
  • 103 Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  • 104 VIB Vesalius Research Center, KU Leuven, Leuven, Belgium
  • 105 Department of Family and Community Medicine, Meharry Medical College, Nashville, Tennessee
  • 106 Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
  • 107 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
  • 108 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
  • 109 Cancer Center and Department of Surgery, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 110 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
  • 111 Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany
  • 112 Section of Cancer Genetics, The Institute of Cancer Research, London, UK
  • 113 Cancer Control Research, British Columbia Cancer Agency, Vancouver, Canada
  • 114 Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK
  • 115 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. Department of Applied Health Research, University College London, London, UK
  • 116 IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy
  • 117 Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France. University Paris-Sud, Villejuif, France
  • 118 International Agency for Research on Cancer, Lyon, France
  • 119 Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  • 120 Department of Cancer Epidemiology, University Hospital, Lund, Sweden
  • 121 Departments of Human Genetics and of Pathology, Leiden University Medical Center, Leiden, the Netherlands
  • 122 Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 123 Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts. Medical College of Xiamen University, Xiamen, China
  • 124 Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, Bulgaria
  • 125 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
  • 126 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
  • 127 Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah
  • 128 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
  • 129 Laboratory of Cancer Genetics and Tumor Biology, Cancer Research and Translational Medicine, Biocenter Oulu, University of Oulu, and Northern Finland Laboratory Centre, Oulu, Finland
  • 130 The University of Texas School of Public Health, Houston, Texas
  • 131 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 132 Department of Hematology-Oncology, National University Health System, Singapore. Cancer Science Institute of Singapore, National University of Singapore, Singapore
  • 133 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
  • 134 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
  • 135 Epidemiology Research Program, American Cancer Society, Atlanta, Georgia
  • 136 Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 137 Department of Obstetrics and Gynecology, and Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
  • 138 Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland
  • 139 Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
  • 140 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany
  • 141 Department of Medical Biochemistry and Genetics Institute of Biomedicine, University of Turku, Turku, Finland
  • 142 Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee
  • 143 Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Department of Pathology, Kuopio University Hospital, Kuopio, Finland
  • 144 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
  • 145 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 146 Institute of Human Genetics, University Hospital Ulm, Ulm, Germany
  • 147 Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 148 Shanghai Cancer Institute, Shanghai, P.R. China
  • 149 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. The Eli and Edythe L. Broad Institute, Cambridge, Massachusetts
  • 150 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada
  • 151 Molecular Cancer Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  • 152 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
  • 153 The Institute of Cancer Research, Sutton, UK. Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK
Cancer Discov, 2016 Sep;6(9):1052-67.
PMID: 27432226 DOI: 10.1158/2159-8290.CD-15-1227

Abstract

Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.

SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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