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

doi:10.1038/ng.3094

Meta-Analysis

. 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

Ali Amin Al Olama¹, Zsofia Kote-Jarai², Sonja I Berndt³, David V Conti⁴, Fredrick Schumacher⁴, Ying Han⁵, Sara Benlloch⁶, Dennis J Hazelett⁴, Zhaoming Wang⁷, Ed Saunders⁸, Daniel Leongamornlert⁸, Sara Lindstrom⁹, Sara Jugurnauth-Little⁸, Tokhir Dadaev⁸, Malgorzata Tymrakiewicz⁸, Daniel O Stram⁴, Kristin Rand⁵, Peggy Wan⁵, Alex Stram⁵, Xin Sheng⁵, Loreall C Pooler⁵, Karen Park⁵, Lucy Xia⁵, Jonathan Tyrer⁶, Laurence N Kolonel¹⁰, Loic Le Marchand¹⁰, Robert N Hoover³, Mitchell J Machiela³, Merideth Yeager³, Laurie Burdette³, Charles C Chung³, Amy Hutchinson³, Kai Yu³, Chee Goh⁸, Mahbubl Ahmed⁸, Koveela Govindasami⁸, Michelle Guy⁸, Teuvo L J Tammela¹¹, Anssi Auvinen¹², Tiina Wahlfors¹³, Johanna Schleutker¹⁴, Tapio Visakorpi¹⁵, Katri A Leinonen¹⁵, Jianfeng Xu¹⁶, Markus Aly¹⁷, Jenny Donovan¹⁸, Ruth C Travis¹⁹, Tim J Key¹⁹, Afshan Siddiq²⁰, Federico Canzian²¹, Kay-Tee Khaw²², Atsushi Takahashi²³, Michiaki Kubo²⁴, Paul Pharoah²⁵, Nora Pashayan²⁵, Maren Weischer²⁶, Borge G Nordestgaard²⁷, Sune F Nielsen²⁷, Peter Klarskov²⁸, Martin Andreas Røder²⁹, Peter Iversen²⁹, Stephen N Thibodeau³⁰, Shannon K McDonnell³⁰, Daniel J Schaid³⁰, Janet L Stanford³¹, Suzanne Kolb³², Sarah Holt³³, Beatrice Knudsen³⁴, Antonio Hurtado Coll³⁵, Susan M Gapstur³⁶, W Ryan Diver³⁶, Victoria L Stevens³⁶, Christiane Maier³⁷, Manuel Luedeke³⁷, Kathleen Herkommer³⁸, Antje E Rinckleb³⁷, Sara S Strom³⁹, Curtis Pettaway⁴⁰, Edward D Yeboah⁴¹, Yao Tettey⁴¹, Richard B Biritwum⁴¹, Andrew A Adjei⁴¹, Evelyn Tay⁴¹, Ann Truelove⁴², Shelley Niwa⁴², Anand P Chokkalingam⁴³, Lisa Cannon-Albright⁴⁴, Cezary Cybulski⁴⁵, Dominika Wokołorczyk⁴⁵, Wojciech Kluźniak⁴⁵, Jong Park⁴⁶, Thomas Sellers⁴⁶, Hui-Yi Lin⁴⁷, William B Isaacs⁴⁸, Alan W Partin⁴⁸, Hermann Brenner⁴⁹, Aida Karina Dieffenbach⁴⁹, Christa Stegmaier⁵⁰, Constance Chen⁹, Edward L Giovannucci⁵¹, Jing Ma⁵², Meir Stampfer⁵³, Kathryn L Penney⁵⁴, Lorelei Mucci⁵⁴, Esther M John⁵⁵, Sue A Ingles⁴, Rick A Kittles⁵⁶, Adam B Murphy⁵⁷, Hardev Pandha⁵⁸, Agnieszka Michael⁵⁸, Andrzej M Kierzek⁵⁸, William Blot⁵⁹, Lisa B Signorello⁵⁴, Wei Zheng⁶⁰, Demetrius Albanes⁶¹, Jarmo Virtamo⁶², Stephanie Weinstein⁶¹, Barbara Nemesure⁶³, John Carpten⁶⁴, Cristina Leske⁶³, Suh-Yuh Wu⁶³, Anselm Hennis⁶⁵, Adam S Kibel⁶⁶, Benjamin A Rybicki⁶⁷, Christine Neslund-Dudas⁶⁷, Ann W Hsing⁵⁵, Lisa Chu⁵⁵, Phyllis J Goodman⁶⁸, Eric A Klein⁶⁹, S Lilly Zheng¹⁶, Jyotsna Batra⁷⁰, Judith Clements⁷⁰, Amanda Spurdle⁷¹, Manuel R Teixeira⁷², Paula Paulo⁷³, Sofia Maia⁷³, Chavdar Slavov⁷⁴, Radka Kaneva⁷⁵, Vanio Mitev⁷⁵, John S Witte⁷⁶, Graham Casey⁴, Elizabeth M Gillanders⁷⁷, Daniella Seminara⁷⁷, Elio Riboli⁷⁸, Freddie C Hamdy⁷⁹, Gerhard A Coetzee⁴, Qiyuan Li⁸⁰, Matthew L Freedman⁸⁰, David J Hunter⁹, Kenneth Muir⁸¹, Henrik Gronberg⁸², David E Neal⁸³, Melissa Southey⁸⁴, Graham G Giles⁸⁵, Gianluca Severi⁸⁶; 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 Cook⁸⁷, Hidewaki Nakagawa⁸⁸, Fredrik Wiklund⁸⁹, Peter Kraft⁹⁰, Stephen J Chanock⁸⁷, Brian E Henderson⁹¹, Douglas F Easton¹, Rosalind A Eeles⁹², Christopher A Haiman⁹¹

Affiliations

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].

PMID: 25217961
PMCID: PMC4383163
DOI: 10.1038/ng.3094

Meta-Analysis

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

Ali Amin Al Olama et al. Nat Genet. 2014 Oct.

. 2014 Oct;46(10):1103-9.

doi: 10.1038/ng.3094. Epub 2014 Sep 14.

Authors

Affiliations

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].

PMID: 25217961
PMCID: PMC4383163
DOI: 10.1038/ng.3094

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.

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Figures

**Figure 1**
Manhattan Plot of genotyped and imputed results from the European ancestry meta-analysis of overall prostate cancer risk. All SNPs within 500kb of known GWAS SNPs are omitted. The green line represents P=5×10^-8. This figure shows all new variants with P<5×10^-8, regardless of the confirmation results (one signal on chr1, one on chr4, one on chr17, and 2 on chr X were not confirmed). Many of the new signals are in close proximity to one another on the same chromosome (see Supplementary Table 6).

**Figure 2**
Manhattan Plot of results from the multiethnic meta-analysis of overall prostate cancer risk. All SNPs within 500kb of known GWAS SNPs are omitted. The green line represents P=5×10^-8. This figure shows all new variants with P<5×10^-8, regardless of the confirmation results, as well as signals that were reported in the European meta-analysis that also reached 5×10^-8 in the multiethnic meta-analysis (see Table 1 and Supplementary Table 6).

**Figure 3**
Regional plots of two novel genome-wide significant loci associated with prostate cancer risk. rs1041449/21q22 (*TMPRSS2* region, left) and rs17694493/9p21 (*CDKN2B-AS1*region, right). Top: SNPs are plotted by their position 500kb on either side of the index SNP (purple diamond) on the chromosome against their association (-log₁₀ P) with prostate cancer from the multiethnic meta-analysis (rs1041449) and European meta-analysis (rs17694493). SNPs surrounding the index SNP are colored to indicate the local LD structure using pairwise r² data from the EUR panel of the 1000 Genomes (March 2012). MIDDLE: Significant peaks from TF and histone modification ChIP-seq experiments in the same genomic window (see **Online Methods**). All ChIP-seq in LNCaP unless otherwise indicated. BOTTOM: Genomic sequence (enclosed in black box) surrounding the SNP (red box) aligned to a LOGO graphic representing the proposed motif disruption.

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Prostate cancer: genetic risk analysis goes global.
Phillips R. Phillips R. Nat Rev Urol. 2014 Dec;11(12):661. doi: 10.1038/nrurol.2014.277. Epub 2014 Sep 30. Nat Rev Urol. 2014. PMID: 25266569 No abstract available.

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References

1. Eeles R, et al. The genetic epidemiology of prostate cancer and its clinical implications. Nat Rev Urol. 2014;11:18–31. - PubMed
1. Eeles RA, et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet. 2013;45:385–91. 391e1–2. - PMC - PubMed
1. Park JH, et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat Genet. 2010;42:570–5. - PMC - PubMed
1. Eeles RA, et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008;40:316–21. - PubMed
1. Gudmundsson J, et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat Genet. 2009;41:1122–6. - PMC - PubMed

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[1] Eeles R, et al. The genetic epidemiology of prostate cancer and its clinical implications. Nat Rev Urol. 2014;11:18–31. - PubMed

[2] Eeles R, et al. The genetic epidemiology of prostate cancer and its clinical implications. Nat Rev Urol. 2014;11:18–31. - PubMed

[3] Eeles RA, et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet. 2013;45:385–91. 391e1–2. - PMC - PubMed

[4] Eeles RA, et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet. 2013;45:385–91. 391e1–2. - PMC - PubMed

[5] Park JH, et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat Genet. 2010;42:570–5. - PMC - PubMed

[6] Park JH, et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat Genet. 2010;42:570–5. - PMC - PubMed

[7] Eeles RA, et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008;40:316–21. - PubMed

[8] Eeles RA, et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet. 2008;40:316–21. - PubMed

[9] Gudmundsson J, et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat Genet. 2009;41:1122–6. - PMC - PubMed

[10] Gudmundsson J, et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat Genet. 2009;41:1122–6. - PMC - PubMed

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

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

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