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Epidemiology and Genomics Research Program

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

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25217961
PMC4383163
Nature genetics
Oct. 1, 2014
Ali Amin Al Olama17, Zsofia Kote-Jarai32, Sonja I Berndt60, David V Conti33, Fredrick Schumacher33, Ying Han6, Sara Benlloch64, Dennis J Hazelett33, Zhaoming Wang73, Ed Saunders12, Daniel Leongamornlert12, Sara Lindstrom31, Sara Jugurnauth-Little12, Tokhir Dadaev12, Malgorzata Tymrakiewicz12, Daniel O Stram33, Kristin Rand6, Peggy Wan6, Alex Stram6, Xin Sheng6, Loreall C Pooler6, Karen Park6, Lucy Xia6, Jonathan Tyrer64, Laurence N Kolonel80, Loic Le Marchand80, Robert N Hoover60, Mitchell J Machiela60, Merideth Yeager60, Laurie Burdette60, Charles C Chung60, Amy Hutchinson60, Kai Yu60, Chee Goh12, Mahbubl Ahmed12, Koveela Govindasami12, Michelle Guy12, Teuvo L J Tammela77, Anssi Auvinen63, Tiina Wahlfors70, Johanna Schleutker23, Tapio Visakorpi28, Katri A Leinonen28, Jianfeng Xu35, Markus Aly82, Jenny Donovan37, Ruth C Travis43, Tim J Key43, Afshan Siddiq41, Federico Canzian45, Kay-Tee Khaw19, Atsushi Takahashi9, Michiaki Kubo51, Paul Pharoah57, Nora Pashayan57, Maren Weischer65, Borge G Nordestgaard67, Sune F Nielsen67, Peter Klarskov92, Martin Andreas Røder16, Peter Iversen16, Stephen N Thibodeau29, Shannon K McDonnell29, Daniel J Schaid29, Janet L Stanford10, Suzanne Kolb25, Sarah Holt27, Beatrice Knudsen14, Antonio Hurtado Coll55, Susan M Gapstur54, W Ryan Diver54, Victoria L Stevens54, Christiane Maier74, Manuel Luedeke74, Kathleen Herkommer5, Antje E Rinckleb74, Sara S Strom47, Curtis Pettaway34, Edward D Yeboah26, Yao Tettey26, Richard B Biritwum26, Andrew A Adjei26, Evelyn Tay26, Ann Truelove21, Shelley Niwa21, Anand P Chokkalingam87, Lisa Cannon-Albright4, Cezary Cybulski42, Dominika Wokołorczyk42, Wojciech Kluźniak42, Jong Park86, Thomas Sellers86, Hui-Yi Lin24, William B Isaacs48, Alan W Partin48, Hermann Brenner2, Aida Karina Dieffenbach2, Christa Stegmaier89, Constance Chen31, Edward L Giovannucci18, Jing Ma66, Meir Stampfer3, Kathryn L Penney71, Lorelei Mucci71, Esther M John76, Sue A Ingles33, Rick A Kittles78, Adam B Murphy75, Hardev Pandha30, Agnieszka Michael30, Andrzej M Kierzek30, William Blot69, Lisa B Signorello71, Wei Zheng39, Demetrius Albanes90, Jarmo Virtamo13, Stephanie Weinstein90, Barbara Nemesure15, John Carpten8, Cristina Leske15, Suh-Yuh Wu15, Anselm Hennis91, Adam S Kibel52, Benjamin A Rybicki53, Christine Neslund-Dudas53, Ann W Hsing76, Lisa Chu76, Phyllis J Goodman11, Eric A Klein58, S Lilly Zheng35, Jyotsna Batra20, Judith Clements20, Amanda Spurdle62, Manuel R Teixeira38, Paula Paulo72, Sofia Maia72, Chavdar Slavov79, Radka Kaneva59, Vanio Mitev59, John S Witte83, Graham Casey33, Elizabeth M Gillanders85, Daniella Seminara85, Elio Riboli1, Freddie C Hamdy7, Gerhard A Coetzee33, Qiyuan Li46, Matthew L Freedman46, David J Hunter31, Kenneth Muir68, Henrik Gronberg49, David E Neal50, Melissa Southey22, Graham G Giles81, Gianluca Severi88, 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, Michael B Cook56, Hidewaki Nakagawa84, Fredrik Wiklund44, Peter Kraft36, Stephen J Chanock56, Brian E Henderson61, Douglas F Easton17, Rosalind A Eeles40, Christopher A Haiman61
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  • 1
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • 2
    1] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2] German Cancer Consortium, Heidelberg, Germany.
  • 3
    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.
  • 4
    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.
  • 5
    Department of Urology, Klinikum Rechts der Isar der Technischen Universität München, Munich, Germany.
  • 6
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • 7
    Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • 8
    Translational Genomics Research Institute, Phoenix, Arizona, USA.
  • 9
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • 10
    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.
  • 11
    Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • 12
    Institute of Cancer Research, London, UK.
  • 13
    Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
  • 14
    Translational Pathology, Cedars-Sinai, Los Angeles, California, USA.
  • 15
    Department of Preventive Medicine, Stony Brook University, Stony Brook, New York, USA.
  • 16
    Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • 17
    1] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [2].
  • 18
    1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
  • 19
    Clinical Gerontology Unit, University of Cambridge, Cambridge, UK.
  • 20
    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.
  • 21
    Westat, Rockville, Maryland, USA.
  • 22
    Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
  • 23
    1] BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland. [2] Department of Medical Biochemistry, Institute of Biomedicine, University of Turku, Turku, Finland.
  • 24
    Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida, USA.
  • 25
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • 26
    1] University of Ghana Medical School, Accra, Ghana. [2] Korle Bu Teaching Hospital, Accra, Ghana.
  • 27
    Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • 28
    Institute of Biomedical Technology/BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.
  • 29
    Mayo Clinic, Rochester, Minnesota, USA.
  • 30
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
  • 31
    Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  • 32
    1] Institute of Cancer Research, London, UK. [2].
  • 33
    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.
  • 34
    Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • 35
    Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • 36
    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].
  • 37
    School of Social and Community Medicine, University of Bristol, Bristol, UK.
  • 38
    1] Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. [2] Biomedical Sciences Institute, University of Porto, Porto, Portugal.
  • 39
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • 40
    1] Institute of Cancer Research, London, UK. [2] Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK. [3].
  • 41
    Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
  • 42
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • 43
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • 44
    1] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. [2].
  • 45
    Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 46
    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • 47
    Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • 48
    James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, Maryland, USA.
  • 49
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • 50
    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.
  • 51
    Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • 52
    Division of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • 53
    Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, USA.
  • 54
    Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.
  • 55
    Prostate Center, Vancouver, British Columbia, Canada.
  • 56
    1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA. [2].
  • 57
    Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • 58
    Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA.
  • 59
    Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria.
  • 60
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA.
  • 61
    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].
  • 62
    Molecular Cancer Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • 63
    Department of Epidemiology, School of Health Sciences, University of Tampere, Tampere, Finland.
  • 64
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • 65
    Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • 66
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 67
    1] Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. [2] Faculty of Healthy and Medical Sciences, University of Copenhagen, Herlev, Denmark.
  • 68
    1] Institute of Population Health, University of Manchester, Manchester, UK. [2] Warwick Medical School, University of Warwick, Coventry, UK.
  • 69
    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.
  • 70
    BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.
  • 71
    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.
  • 72
    Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
  • 73
    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.
  • 74
    Department of Urology, University Hospital Ulm, Ulm, Germany.
  • 75
    Department of Urology, Northwestern University, Chicago, Illinois, USA.
  • 76
    1] Cancer Prevention Institute of California, Fremont, California, USA. [2] Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.
  • 77
    Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
  • 78
    Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
  • 79
    Department of Urology, Medical University-Sofia, Sofia, Bulgaria.
  • 80
    Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
  • 81
    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.
  • 82
    1] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. [2] Department of Clinical Sciences at Danderyds Hospital, Stockholm, Sweden.
  • 83
    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.
  • 84
    1] Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan. [2].
  • 85
    Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA.
  • 86
    Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
  • 87
    School of Public Health, University of California, Berkeley, Berkeley, California, USA.
  • 88
    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.
  • 89
    Saarland Cancer Registry, Saarbrücken, Germany.
  • 90
    Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institute of Health, Bethesda, Maryland, USA.
  • 91
    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.
  • 92
    Department of Urology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Genetic Loci, Genome-Wide Association Study, Genotype, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Genetic Predisposition to Disease, Male, Risk Assessment, Humans, Risk Factors
R01 CA068578, R01 ES011126, G2011/36, R01 CA084979, P50 CA140388, G2012/48, U01 CA127298, U01 CA089600, P30 ES007784, P30 CA068485, R01 CA088164, S06 GM008016, U01 CA136792, RC2 CA148085, U01 HG004446, P01 GM099568, U01 HG004726, R01 CA056678, R01 CA072818, R01 CA082664, U19 CA148112, R01 CA092579, 13065, U10 CA037429, UG1 CA189974, UM1 CA182883, R01 CA136924, P30 CA076292, R01 CA128813, P30 CA042014, 14136, R01 CA128978, R01 CA092447, U19 CA148537, U19 CA148065, G1000143, 10124, G0900871, 11022, 10118, G0401527, U01 CA063464, R37 CA054281, U01 CA098216, U01 CA098233, U01 CA098758, U01 CA098710
Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Røder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokołorczyk D, Kluźniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G, 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 MB, Nakagawa H, Wiklund F, Kraft P, Chanock SJ, Henderson BE, Easton DF, Eeles RA, Haiman CA. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nature genetics. 2014 Oct.

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.
Last Updated: 30 Apr, 2026