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Cancer Discov. 2016 Sep;6(9):1052-67. doi: 10.1158/2159-8290.CD-15-1227. Epub 2016 Jul 17.

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 SP1, Beesley J2, Amin Al Olama A3, Michailidou K3, Tyrer J4, Kote-Jarai Z5, Lawrenson K6, Lindstrom S7, Ramus SJ6, Thompson DJ3; ABCTB Investigators, Kibel AS8, Dansonka-Mieszkowska A9, Michael A10, Dieffenbach AK11, Gentry-Maharaj A12, Whittemore AS13, Wolk A14, Monteiro A15, Peixoto A16, Kierzek A10, Cox A17, Rudolph A18, Gonzalez-Neira A19, Wu AH6, Lindblom A20, Swerdlow A21; AOCS Study Group & Australian Cancer Study (Ovarian Cancer); APCB BioResource, Ziogas A22, Ekici AB23, Burwinkel B24, Karlan BY25, Nordestgaard BG26, Blomqvist C27, Phelan C15, McLean C28, Pearce CL29, Vachon C30, Cybulski C31, Slavov C32, Stegmaier C33, Maier C34, Ambrosone CB35, Høgdall CK36, Teerlink CC37, Kang D38, Tessier DC39, Schaid DJ40, Stram DO6, Cramer DW41, Neal DE42, Eccles D43, Flesch-Janys D44, Edwards DR45, Wokozorczyk D31, Levine DA46, Yannoukakos D47, Sawyer EJ48, Bandera EV49, Poole EM50, Goode EL30, Khusnutdinova E51, Høgdall E52, Song F53, Bruinsma F54, Heitz F55, Modugno F56, Hamdy FC57, Wiklund F58, Giles GG59, Olsson H60, Wildiers H61, Ulmer HU62, Pandha H10, Risch HA63, Darabi H58, Salvesen HB64, Nevanlinna H65, Gronberg H58, Brenner H66, Brauch H67, Anton-Culver H22, Song H4, Lim HY68, McNeish I69, Campbell I70, Vergote I71, Gronwald J31, Lubiński J31, Stanford JL72, Benítez J19, Doherty JA73, Permuth JB15, Chang-Claude J18, Donovan JL74, Dennis J3, Schildkraut JM75, Schleutker J76, Hopper JL77, Kupryjanczyk J9, Park JY15, Figueroa J78, Clements JA79, Knight JA80, Peto J81, Cunningham JM82, Pow-Sang J15, Batra J79, Czene K58, Lu KH83, Herkommer K84, Khaw KT85; kConFab Investigators, Matsuo K86, Muir K87, Offitt K88, Chen K53, Moysich KB89, Aittomäki K90, Odunsi K91, Kiemeney LA92, Massuger LF93, Fitzgerald LM54, Cook LS94, Cannon-Albright L95, Hooning MJ96, Pike MC97, Bolla MK3, Luedeke M34, Teixeira MR98, Goodman MT99, Schmidt MK100, Riggan M101, Aly M102, Rossing MA72, Beckmann MW103, Moisse M104, Sanderson M105, Southey MC106, Jones M107, Lush M3, Hildebrandt MA108, Hou MF109, Schoemaker MJ107, Garcia-Closas M110, Bogdanova N111, Rahman N112; NBCS Investigators, Le ND113, Orr N114, Wentzensen N78, Pashayan N115, Peterlongo P116, Guénel P117, Brennan P118, Paulo P16, Webb PM119, Broberg P120, Fasching PA103, Devilee P121, Wang Q3, Cai Q122, Li Q123, Kaneva R124, Butzow R125, Kopperud RK64, Schmutzler RK126, Stephenson RA127, MacInnis RJ128, Hoover RN78, Winqvist R129, Ness R130, Milne RL128, Travis RC131, Benlloch S3, Olson SH97, McDonnell SK40, Tworoger SS50, Maia S16, Berndt S78, Lee SC132, Teo SH133, Thibodeau SN40, Bojesen SE134, Gapstur SM135, Kjær SK136, Pejovic T137, Tammela TL138; GENICA Network; PRACTICAL consortium, Dörk T139, Brüning T140, Wahlfors T141, Key TJ131, Edwards TL142, Menon U12, Hamann U62, Mitev V124, Kosma VM143, Setiawan VW6, Kristensen V144, Arndt V145, Vogel W146, Zheng W122, Sieh W13, Blot WJ147, Kluzniak W31, Shu XO122, Gao YT148, Schumacher F6, Freedman ML149, Berchuck A101, Dunning AM4, Simard J150, Haiman CA6, Spurdle A151, Sellers TA15, Hunter DJ7, Henderson BE6, Kraft P7, Chanock SJ78, Couch FJ82, Hall P58, Gayther SA6, Easton DF152, Chenevix-Trench G2, Eeles R153, Pharoah PD152, Lambrechts D104.

Author information

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.

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.

PMID:
27432226
PMCID:
PMC5010513
[Available on 2017-03-01]
DOI:
10.1158/2159-8290.CD-15-1227
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors disclose no potential conflicts of interest.

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