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

  • David V. Conti
  • , Burcu F. Darst
  • , Lilit C. Moss
  • , Edward J. Saunders
  • , Xin Sheng
  • , Alisha Chou
  • , Fredrick R. Schumacher
  • , Ali Amin Al Olama
  • , Sara Benlloch
  • , Tokhir Dadaev
  • , Mark N. Brook
  • , Ali Sahimi
  • , Thomas J. Hoffmann
  • , Atushi Takahashi
  • , Koichi Matsuda
  • , Yukihide Momozawa
  • , Masashi Fujita
  • , Kenneth Muir
  • , Artitaya Lophatananon
  • , Peggy Wan
  • Loic Le Marchand, Lynne R. Wilkens, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Johanna Schleutker, Teuvo L.J. Tammela, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokołorczyk, Jan Lubiński, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Martin Andreas Røder, Peter Iversen, Jyotsna Batra, Suzanne Chambers, Leire Moya, Lisa Horvath, Judith A. Clements, Wayne Tilley, Gail P. Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordström, Nora Pashayan, Alison M. Dunning, Maya Ghoussaini, Ruth C. Travis, Tim J. Key, Elio Riboli, Jong Y. Park, Thomas A. Sellers, Hui Yi Lin, Demetrius Albanes, Stephanie J. Weinstein, Lorelei A. Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David J. Hunter, Kathryn L. Penney, Constance Turman, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Marie Élise Parent, Janet L. Stanford, Elaine A. Ostrander, Milan S. Geybels, Stella Koutros, Laura E.Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L. Andriole, Robert N. Hoover, Mitchell J. Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J. Blot, Wei Zheng, Edward D. Yeboah, James E. Mensah, Yong Jie Lu, Hong Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan Chao Zhao, Zan Sun, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Catharine M.L. West, Neil Burnet, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S. Kibel, Bettina F. Drake, Olivier Cussenot, Géraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M. John, Eli Marie Grindedal, Lovise Maehle, Kay Tee Khaw, Sue A. Ingles, Mariana C. Stern, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Barry S. Rosenstein, Sarah L. Kerns, Harry Ostrer, Manuel R. Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T. Bensen, Elizabeth T.H. Fontham, James Mohler, Jack A. Taylor, Manolis Kogevinas, Javier Llorca, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C. Teerlink, Chad D. Huff, Sara S. Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J. Leach, Brandi Weaver, Hermann Brenner, Katarina Cuk, Bernd Holleczek, Kai Uwe Saum, Eric A. Klein, Ann W. Hsing, Rick A. Kittles, Adam B. Murphy, Christopher J. Logothetis, Jeri Kim, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, William B. Isaacs, Barbara Nemesure, Anselm J.M. Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo Hwang Teo, Lisa F. Newcomb, Daniel W. Lin, Jay H. Fowke, Christine Neslund-Dudas, Benjamin A. Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, William S. Bush, Melinda C. Aldrich, Dana C. Crawford, Shiv Srivastava, Jennifer C. Cullen, Gyorgy Petrovics, Graham Casey, Monique J. Roobol, Guido Jenster, Ron H.N. van Schaik, Jennifer J. Hu, Maureen Sanderson, Rohit Varma, Roberta McKean-Cowdin, Mina Torres, Nicholas Mancuso, Sonja I. Berndt, Stephen K. Van Den Eeden, Douglas F. Easton, Stephen J. Chanock, Michael B. Cook, Fredrik Wiklund, Hidewaki Nakagawa, John S. Witte, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman
  • University of Southern California
  • The Institute of Cancer Research
  • Case Western Reserve University
  • University of Cambridge
  • University of California at San Francisco
  • RIKEN
  • National Cerebral and Cardiovascular Center
  • The University of Tokyo
  • Biobank
  • University of Manchester
  • University of Warwick
  • University of Hawai'i at Mānoa
  • American Cancer Society
  • University of Turku
  • Tampere University
  • Cancer Council Victoria
  • University of Melbourne
  • Monash University
  • Pomeranian Medical University in Szczecin
  • University of Oxford
  • Cancer Research UK
  • University of Bristol
  • University of Copenhagen
  • Queensland University of Technology
  • Translational Research Institute Australia
  • University of Technology Sydney
  • Camperdown
  • Garvan Institute of Medical Research
  • Adelaide University
  • Peter Maccallum Cancer Centre
  • Karolinska Institutet
  • SDS Life Science
  • Stockholm County Council
  • University College London
  • Wellcome Sanger Institute
  • Imperial College London
  • Moffitt Cancer Center
  • Louisiana State University Health Sciences Center
  • National Institutes of Health
  • Harvard University
  • University of Washington
  • Brigham and Women’s Hospital
  • Fred Hutchinson Cancer Research Center
  • CHRISTUS Santa Rosa Hospital
  • Princess Margaret Cancer Centre
  • University of Toronto
  • Institut national de la recherche scientifique
  • University of Montreal
  • Uppsala University
  • Washington University St. Louis
  • Aarhus University
  • Vanderbilt University
  • International Epidemiology Institute
  • University of Ghana
  • Korle Bu Teaching Hospital
  • Queen Mary University of London
  • Naval Medical University
  • Nanjing Medical University
  • The First Affiliated Hospital of Zhengzhou University
  • Southern Medical University
  • China Medical University
  • Mayo Clinic Rochester, MN
  • Humangenetik Tuebingen
  • Ulm University
  • Genetikum
  • Sorbonne Université
  • Tenon Hospital
  • Institut national de la santé et de la recherche médicale
  • Université Paris-Saclay
  • Stanford University
  • University of Oslo
  • Fundación Pública Galega Medicina Xenómica
  • Instituto de Investigación Sanitaria de Santiago de Compostela
  • Centro de Investigación en Red de Enfermedades Raras (CIBERER)
  • Complejo Hospitalario Universitario de Santiago
  • Icahn School of Medicine at Mount Sinai
  • University of Rochester
  • Albert Einstein College of Medicine
  • Instituto Português de Oncologia do Porto Francisco Gentil E.P.E.
  • University of Porto
  • Uro Care
  • University of North Carolina at Chapel Hill
  • University of North Carolina at Chapel Hill
  • Roswell Park Cancer Institute
  • ISGlobal
  • Hospital del Mar
  • Pompeu Fabra University
  • CIBER Epidemiología y Salud Pública (CIBERESP)
  • Universidad de Cantabria
  • University of Utah
  • VA Medical Center
  • University of Texas MD Anderson Cancer Center
  • University Rennes
  • Université des Antilles
  • Medical University Sofia
  • University of Texas Health Science Center at San Antonio
  • German Cancer Research Center
  • Saarland Cancer Registry
  • Cleveland Clinic Foundation
  • City of Hope National Med Center
  • Northwestern University
  • Johns Hopkins University
  • Stony Brook University
  • The University of the West Indies
  • University of Surrey
  • Ghent University
  • NorthShore University HealthSystem
  • University of Malaya
  • Sime Darby Berhad
  • University of Tennessee Health Science Center
  • Henry Ford Health System
  • University of Zagreb
  • University of Hamburg
  • University of Alberta
  • Cross Cancer Institute
  • Molecular Endocrinology Laboratory
  • KU Leuven
  • University of California at San Diego
  • University Hospital Complex of Vigo
  • University of Southampton
  • Uniformed Services University of the Health Sciences
  • University of Virginia
  • Erasmus University Rotterdam
  • University of Miami
  • Meharry Medical College
  • CHA Hollywood Presbyterian Medical Center
  • Kaiser Permanente
  • Royal Marsden NHS Foundation Trust

Research output: Contribution to journalArticlepeer-review

358 Scopus citations

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.

Original languageEnglish
Pages (from-to)65-75
Number of pages11
JournalNature Genetics
Volume53
Issue number1
DOIs
StatePublished - Jan 2021

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