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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

About this Publication
Title
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.
Pubmed ID
33398198 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Nat Genet. 2021 Jan 4
Authors
Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, Schumacher FR, Olama AAA, Benlloch S, Dadaev T, Brook MN, Sahimi A, Hoffmann TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Muir K, Lophatananon A, Wan P, ...show more Le Marchand L, Wilkens LR, Stevens VL, Gapstur SM, Carter BD, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokołorczyk D, Lubiński J, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder MA, Iversen P, Batra J, Chambers S, Moya L, Horvath L, Clements JA, Tilley W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordström T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein SJ, 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, Geybels MS, Koutros S, Freeman LEB, 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, Burnet N, 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, Fontham ETH, Mohler J, Taylor JA, Kogevinas M, Llorca J, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Weaver B, Brenner H, Cuk K, Holleczek B, Saum KU, 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 C, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, 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 JC, Petrovics G, Casey G, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Varma R, McKean-Cowdin R, Torres M, Mancuso N, Berndt SI, Van Den Eeden SK, Easton DF, Chanock SJ, Cook MB, Wiklund F, Nakagawa H, Witte JS, Eeles RA, Kote-Jarai Z, Haiman CA
Affiliations
  • Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • The Institute of Cancer Research, London, UK.
  • Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
  • Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
  • Laboratory for Genotyping Development, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
  • Laboratory for Cancer Genomics, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
  • 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.
...show more
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Behavioral and Epidemiology Research Group, Research Program, American Cancer Society, Atlanta, GA, USA.
  • Institute of Biomedicine, University of Turku, Turku, Finland.
  • Department of Urology, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, 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.
  • Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, 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.
  • Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
  • University of Technology, Sydney, New South Wales, Australia.
  • Chris O'Brien Lifehouse (COBLH), Camperdown, Sydney, New South Wales, Australia.
  • Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
  • Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • Department of Applied Health Research, University College London, London, UK.
  • Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Cambridge, UK.
  • Open Targets, Wellcome Sanger Institute, Hinxton, 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, Institut National de la Recherche Scientifique, 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.
  • Washington University School of Medicine, St Louis, MI, 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 Province, The People's Hospital of China Medical University, Shenyang, China.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Division of Biomedical Statistics and Informatics, 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.
  • Division of Cancer Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Science Centre, and The Christie 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, Germany.
  • genetikum, Neu-Ulm, Germany.
  • Division of Urologic Surgery, Brigham and Womens Hospital, Boston, MA, USA.
  • Sorbonne Universite, Tenon Hospital, Paris, France.
  • Exposome and Heredity, CESP (UMR 1018), Paris-Saclay Medical School, Paris-Saclay University, Inserm, Gustave Roussy, Villejuif, France.
  • CESP (UMR 1018), Paris-Saclay Medical School, Paris-Saclay University, Inserm, Villejuif, France.
  • Department of Medicine, Division of Oncology, 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 Preventive Medicine, 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 and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, USA.
  • Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), 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 (CIBERESP), Madrid, Spain.
  • Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
  • University of Rennes, Inserm, EHESP, Irset (Research Institute for Environmental and Occupational Health), Rennes, France.
  • CHU de Pointe-à-Pitre, University of the French Antilles, University of Rennes, Inserm, EHESP, Irset (Research Institute for Environmental and Occupational Health), 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 Urology, Cancer Therapy and Research 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.
  • Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Division of Health Equities, Department of Population Sciences, City of Hope, Duarte, CA, USA.
  • Department of Urology, Northwestern University, Chicago, IL, USA.
  • Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 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.
  • Faculty of Health and Medical Sciences, The University of Surrey, Guildford, UK.
  • Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium.
  • Department of Radiotherapy, Ghent University Hospital, Gent, 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 (CRM), Outpatient Centre, Subang Jaya Medical Centre, Subang Jaya, Malaysia.
  • Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
  • Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
  • Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
  • Department of Oncology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, 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.
  • Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, 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 (IISGS), Vigo, Spain.
  • Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
  • The University of Southampton, Southampton General Hospital, Southampton, UK.
  • Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Center for Prostate Disease Research, Uniformed Services University, Bethesda, MD, USA.
  • Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • 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.
  • Southern California Eye Institute, CHA Hollywood Presbyterian Medical Center, Los Angeles, CA, USA.
  • Division of Research, Kaiser Permanente, Northern California, Oakland, CA, USA.
  • Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA. haiman@usc.edu.
Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

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