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Nat Genet. 2014 Oct;46(10):1103-9. doi: 10.1038/ng.3094. Epub 2014 Sep 14.

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

Al Olama AA1, Kote-Jarai Z2, Berndt SI3, Conti DV4, Schumacher F4, Han Y5, Benlloch S6, Hazelett DJ4, Wang Z7, Saunders E8, Leongamornlert D8, Lindstrom S9, Jugurnauth-Little S8, Dadaev T8, Tymrakiewicz M8, Stram DO4, Rand K5, Wan P5, Stram A5, Sheng X5, Pooler LC5, Park K5, Xia L5, Tyrer J6, Kolonel LN10, Le Marchand L10, Hoover RN3, Machiela MJ3, Yeager M3, Burdette L3, Chung CC3, Hutchinson A3, Yu K3, Goh C8, Ahmed M8, Govindasami K8, Guy M8, Tammela TL11, Auvinen A12, Wahlfors T13, Schleutker J14, Visakorpi T15, Leinonen KA15, Xu J16, Aly M17, Donovan J18, Travis RC19, Key TJ19, Siddiq A20, Canzian F21, Khaw KT22, Takahashi A23, Kubo M24, Pharoah P25, Pashayan N25, Weischer M26, Nordestgaard BG27, Nielsen SF27, Klarskov P28, Røder MA29, Iversen P29, Thibodeau SN30, McDonnell SK30, Schaid DJ30, Stanford JL31, Kolb S32, Holt S33, Knudsen B34, Coll AH35, Gapstur SM36, Diver WR36, Stevens VL36, Maier C37, Luedeke M37, Herkommer K38, Rinckleb AE37, Strom SS39, Pettaway C40, Yeboah ED41, Tettey Y41, Biritwum RB41, Adjei AA41, Tay E41, Truelove A42, Niwa S42, Chokkalingam AP43, Cannon-Albright L44, Cybulski C45, Wokołorczyk D45, Kluźniak W45, Park J46, Sellers T46, Lin HY47, Isaacs WB48, Partin AW48, Brenner H49, Dieffenbach AK49, Stegmaier C50, Chen C9, Giovannucci EL51, Ma J52, Stampfer M53, Penney KL54, Mucci L54, John EM55, Ingles SA4, Kittles RA56, Murphy AB57, Pandha H58, Michael A58, Kierzek AM58, Blot W59, Signorello LB54, Zheng W60, Albanes D61, Virtamo J62, Weinstein S61, Nemesure B63, Carpten J64, Leske C63, Wu SY63, Hennis A65, Kibel AS66, Rybicki BA67, Neslund-Dudas C67, Hsing AW55, Chu L55, Goodman PJ68, Klein EA69, Zheng SL16, Batra J70, Clements J70, Spurdle A71, Teixeira MR72, Paulo P73, Maia S73, Slavov C74, Kaneva R75, Mitev V75, Witte JS76, Casey G4, Gillanders EM77, Seminara D77, Riboli E78, Hamdy FC79, Coetzee GA4, Li Q80, Freedman ML80, Hunter DJ9, Muir K81, Gronberg H82, Neal DE83, Southey M84, Giles GG85, Severi G86; Breast and Prostate Cancer Cohort Consortium (BPC3); PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; COGS (Collaborative Oncological Gene-environment Study) Consortium; GAME-ON/ELLIPSE Consortium, Cook MB87, Nakagawa H88, Wiklund F89, Kraft P90, Chanock SJ87, Henderson BE91, Easton DF1, Eeles RA92, Haiman CA91.

Author information

1
1] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [2].
2
1] Institute of Cancer Research, London, UK. [2].
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA.
4
1] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. [2] Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
5
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
6
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
7
1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick, Maryland, USA.
8
Institute of Cancer Research, London, UK.
9
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
10
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
11
Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
12
Department of Epidemiology, School of Health Sciences, University of Tampere, Tampere, Finland.
13
BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.
14
1] BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland. [2] Department of Medical Biochemistry, Institute of Biomedicine, University of Turku, Turku, Finland.
15
Institute of Biomedical Technology/BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.
16
Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
17
1] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. [2] Department of Clinical Sciences at Danderyds Hospital, Stockholm, Sweden.
18
School of Social and Community Medicine, University of Bristol, Bristol, UK.
19
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
20
Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
21
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
22
Clinical Gerontology Unit, University of Cambridge, Cambridge, UK.
23
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
24
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
25
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
26
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
27
1] Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. [2] Faculty of Healthy and Medical Sciences, University of Copenhagen, Herlev, Denmark.
28
Department of Urology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
29
Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
30
Mayo Clinic, Rochester, Minnesota, USA.
31
1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
32
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
33
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
34
Translational Pathology, Cedars-Sinai, Los Angeles, California, USA.
35
Prostate Center, Vancouver, British Columbia, Canada.
36
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
37
Department of Urology, University Hospital Ulm, Ulm, Germany.
38
Department of Urology, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany.
39
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
40
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
41
1] University of Ghana Medical School, Accra, Ghana. [2] Korle Bu Teaching Hospital, Accra, Ghana.
42
Westat, Rockville, Maryland, USA.
43
School of Public Health, University of California, Berkeley, Berkeley, California, USA.
44
1] Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. [2] George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
45
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
46
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
47
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida, USA.
48
James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, Maryland, USA.
49
1] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2] German Cancer Consortium, Heidelberg, Germany.
50
Saarland Cancer Registry, Saarbrücken, Germany.
51
1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
52
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
53
1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
54
1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
55
1] Cancer Prevention Institute of California, Fremont, California, USA. [2] Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.
56
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
57
Department of Urology, Northwestern University, Chicago, Illinois, USA.
58
Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
59
1] International Epidemiology Institute, Rockville, Maryland, USA. [2] Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
60
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
61
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA.
62
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
63
Department of Preventive Medicine, Stony Brook University, Stony Brook, New York, USA.
64
Translational Genomics Research Institute, Phoenix, Arizona, USA.
65
1] Department of Preventive Medicine, Stony Brook University, Stony Brook, New York, USA. [2] Chronic Disease Research Centre, University of the West Indies, Bridgetown, Barbados.
66
Division of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
67
Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, USA.
68
Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
69
Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.
70
Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Translational Research Institute, Brisbane, Queensland, Australia.
71
Molecular Cancer Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
72
1] Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. [2] Biomedical Sciences Institute, University of Porto, Porto, Portugal.
73
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
74
Department of Urology, Medical University-Sofia, Sofia, Bulgaria.
75
Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria.
76
1] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA. [2] Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
77
Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA.
78
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
79
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
80
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
81
1] Institute of Population Health, University of Manchester, Manchester, UK. [2] Warwick Medical School, University of Warwick, Coventry, UK.
82
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
83
1] Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK. [2] Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
84
Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
85
1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
86
1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia. [3] Human Genetics Foundation, Torino, Italy.
87
1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA. [2].
88
1] Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan. [2].
89
1] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. [2].
90
1] Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3].
91
1] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. [2] Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA. [3].
92
1] Institute of Cancer Research, London, UK. [2] Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK. [3].

Abstract

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

PMID:
25217961
PMCID:
PMC4383163
DOI:
10.1038/ng.3094
[Indexed for MEDLINE]
Free PMC Article

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