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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

About this Publication
Title
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
Pubmed ID
37945903 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Nat Genet. 2023 Dec; Volume 55 (Issue 12): Pages 2065-2074
Authors
Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, Darst BF, Sheng X, Xu Y, Chou AJ, Benlloch S, Dadaev T, Brook MN, Plym A, Sahimi A, Hoffman TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, ...show more Laisk T, Figuerêdo J, Muir K, Ito S, Liu X, Biobank Japan Project, Uchio Y, Kubo M, Kamatani Y, Lophatananon A, Wan P, Andrews C, Lori A, Choudhury PP, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokolorczyk D, Lubinski J, Rentsch CT, Cho K, Mcmahon BH, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder A, Stroomberg HV, Batra J, Chambers S, Horvath L, Clements JA, Tilly W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordstrom T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein S, Cook MB, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Koutros S, Beane Freeman LE, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Butler EN, Mohler JL, Taylor JA, Kogevinas M, Dierssen-Sotos T, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Pilie P, Yu Y, Bohlender RJ, Gu J, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Brenner H, Chen X, Holleczek B, Schöttker B, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas CM, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Abraham A, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen J, Petrovics G, Casey G, Wang Y, Tettey Y, Lachance J, Tang W, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Yamoah K, Govindasami K, Chokkalingam AP, Keaton JM, Hellwege JN, Clark PE, Jalloh M, Gueye SM, Niang L, Ogunbiyi O, Shittu O, Amodu O, Adebiyi AO, Aisuodionoe-Shadrach OI, Ajibola HO, Jamda MA, Oluwole OP, Nwegbu M, Adusei B, Mante S, Darkwa-Abrahams A, Diop H, Gundell SM, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Kachuri L, Varma R, McKean-Cowdin R, Torres M, Preuss MH, Loos RJF, Zawistowski M, Zöllner S, Lu Z, Van Den Eeden SK, Easton DF, Ambs S, Edwards TL, Mägi R, Rebbeck TR, Fritsche L, Chanock SJ, Berndt SI, Wiklund F, Nakagawa H, Witte JS, Gaziano JM, Justice AC, Mancuso N, Terao C, Eeles RA, Kote-Jarai Z, Madduri RK, Conti DV, Haiman CA
Affiliations
  • Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Argonne National Laboratory, Lemont, IL, USA.
  • The Institute of Cancer Research, London, UK.
  • School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Department of Computational Biology and Medical Sciences, Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
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  • Laboratory for Genotyping Development, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
  • Laboratory for Cancer Genomics, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
  • Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
  • Department of Orthopaedics, Shimane University, Izumo, Japan.
  • Laboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
  • RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA.
  • Department of Population Science, American Cancer Society, Kennesaw, GA, USA.
  • Surveillance & Health Science Department, American Cancer Society, Kennesaw, GA, USA.
  • Institute of Biomedicine, University of Turku, Turku, Finland.
  • Department of Urology, Tampere University Hospital, Tampere, Finland.
  • Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
  • International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Yale School of Medicine, New Haven, CT, USA.
  • Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Theoretical Biology Division, Los Alamos National Lab, Los Alamos, NM, USA.
  • Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, UK.
  • Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
  • Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia.
  • University of Technology, Sydney, New South Wales, Australia.
  • Chris O'Brien Lifehouse, Camperdown, Sydney, New South Wales, Australia.
  • Translational Research Institute, Brisbane, Queensland, Australia.
  • Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide, Adelaide, South Australia, Australia.
  • Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.
  • Department of Applied Health Research, University College London, London, UK.
  • Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, Cambridge, UK.
  • Open Targets, Wellcome Sanger Institute, Saffron Walden, UK.
  • Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
  • School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
  • SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • CHRISTUS Santa Rosa Hospital-Medical Center, San Antonio, TX, USA.
  • Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Division of Urology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Laval, Quebec, Canada.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Brady Urological Institute in National Capital Region, Johns Hopkins University, Baltimore, MD, USA.
  • Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • University of Ghana Medical School, Accra, Ghana.
  • Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, UK.
  • Second Military Medical University, Shanghai, China.
  • Wuxi Second Hospital, Nanjing Medical University, Wuxi, China.
  • Department of Urology, First Affiliated Hospital, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • The People's Hospital of Liaoning Proviouce, The People's Hospital of China Medical University, Shenyang, China.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK.
  • University of Cambridge Department of Oncology, Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • Humangenetik Tuebingen, Tuebingen, Germany.
  • Department of Urology, University Hospital Ulm, Ulm, Germany.
  • Division of Urologic Surgery, Brigham and Womens Hospital, Boston, MA, USA.
  • Washington University School of Medicine, St. Louis, MO, USA.
  • GRC 5 Predictive Onco-Urology, Sorbonne Université, Paris, France.
  • Exposome and Heredity, CESP (UMR 1018), Paris-Saclay Medical School, Paris-Saclay University, Inserm, Gustave Roussy, Villejuif, France.
  • Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
  • Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
  • Clinical Gerontology Unit, University of Cambridge, Cambridge, UK.
  • Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Fundación Pública Galega Medicina Xenómica, Santiago de Compostela, Spain.
  • Department of Radiation Oncology, Complexo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain.
  • Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Department of Laboratory Genetics, Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center, Porto, Portugal.
  • Cancer Genetics Group, IPO Porto Research Center (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center, Porto, Portugal.
  • Uro Care, Kampala, Uganda.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
  • ISGlobal, Barcelona, Spain.
  • CIBER Epidemiología y Salud Pública, Madrid, Spain.
  • Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Univ Rennes, Inserm, EHESP, Institut de recherche en santé, environnement et travail, Rennes, France.
  • CHU de Pointe-à-Pitre, Univ Antilles, Univ Rennes, Inserm, EHESP, Institut de recherche en santé, environnement et travail, Pointe-à-Pitre, France.
  • Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria.
  • Department of Urology and Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria.
  • Department of Cell Systems and Anatomy and Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Saarland Cancer Registry, Saarbrücken, Germany.
  • Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
  • City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • Department of Urology, Northwestern University, Chicago, IL, USA.
  • Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
  • James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA.
  • Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, USA.
  • Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • The University of Surrey, Guildford, UK.
  • Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Ghent, Belgium.
  • Department of Radiotherapy, Ghent University Hospital, Ghent, Belgium.
  • Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
  • Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Cancer Research Malaysia, Outpatient Centre, Subang Jaya Medical Centre, Subang Jaya, Malaysia.
  • Department of Preventive Medicine, Division of Epidemiology, The University of Tennessee Health Science Center, Memphis, TN, USA.
  • Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
  • Division of Medical Oncology, Urogenital Unit, Department of Oncology, University Hospital Centre Zagreb, Zagreb, Croatia.
  • Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Urology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
  • Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Department of Cellular and Molecular Medicine, Molecular Endocrinology Laboratory, Leuven, Belgium.
  • Department of Urology, University Hospitals Leuven, Leuven, Belgium.
  • Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saúde, SERGAS, Santiago de Compostela, Spain.
  • Genetic Oncology Unit, CHUVI Hospital, Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica Galicia Sur, Vigo, Spain.
  • Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
  • Scientific Education Support, Thames Ditton, Surrey, Formerly Cancer Sciences, University of Southampton, Southampton, UK.
  • School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.
  • Scientific Education Support, Thames Ditton, UK.
  • Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
  • Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington DC, USA.
  • Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Department of Public Health Science, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Korle Bu Teaching Hospital, Accra, Ghana.
  • Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Department of Pathology, University of Ghana Medical School, Accra, Ghana.
  • Westat, Rockville, MD, USA.
  • School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Atrium Health/Levine Cancer Institute, Charlotte, NC, USA.
  • Hôpital Général Idrissa Pouye, Dakar, Senegal.
  • Department of Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
  • Department of Surgery, College of Medicine, University of Ibadan and Univerity College Hospital, Ibadan, Nigeria.
  • Institute of Child Health, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria.
  • Clinical Epidemiology Unit, Department of Community Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
  • College of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, Nigeria.
  • 37 Military Hospital, Accra, Ghana.
  • Laboratoires Bacteriologie et Virologie, Hôpital Aristide Le Dantec, Dakar, Senegal.
  • Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • The University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
  • Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
  • Department of Epidemiology and Population Health, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Southern California Eye Institute, CHA Hollywood Presbyterian Medical Center, Los Angeles, CA, USA.
  • The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Division of Research, Kaiser Permanente, Oakland, CA, USA.
  • Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
  • Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. haiman@usc.edu.
Abstract

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

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