Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07

AUTHORS

Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt, Sara Benlloch, Mahbubl Ahmed, Edward J. Saunders, Tokhir Dadaev, Daniel Leongamornlert, Ezequiel Anokian, Clara Cieza-Borrella, Chee Goh, Mark N. Brook, Xin Sheng, Laura Fachal, Joe Dennis, Jonathan Tyrer, Kenneth Muir, Artitaya Lophatananon, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Jyotsna Batra, Suzanne Chambers, Leire Moya, Judith Clements, Lisa Horvath, Wayne Tilley, Gail P. Risbridger, Henrik Gronberg, Markus Aly, Tobias Nordström, Paul Pharoah, Nora Pashayan, Johanna Schleutker, Teuvo L. J. Tammela, Csilla Sipeky, Anssi Auvinen, Demetrius Albanes, Stephanie Weinstein, Alicja Wolk, Niclas Håkansson, Catharine M. L. West, Alison M. Dunning, Neil Burnet, Lorelei A. Mucci, Edward Giovannucci, Gerald L. Andriole, Olivier Cussenot, Géraldine Cancel-Tassin, Stella Koutros, Laura E. Beane Freeman, Karina Dalsgaard Sorensen, Torben Falck Orntoft, Michael Borre, Lovise Maehle, Eli Marie Grindedal, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Ruth C. Travis, Tim J. Key, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Sue Ann Ingles, Mariana C. Stern, Barry S. Rosenstein, Sarah L. Kerns, Harry Ostrer, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Xin Guo, Guomin Wang, Zan Sun, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Liesel M. FitzGerald, Adam S. Kibel, Bettina F. Drake, Ana Vega, Antonio Gómez-Caamaño, Robert Szulkin, Martin Eklund, Manolis Kogevinas, Javier Llorca, Gemma Castaño-Vinyals, Kathryn L. Penney, Meir Stampfer, Jong Y. Park, Thomas A. Sellers, Hui-Yi Lin, Janet L. Stanford, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Elaine A. Ostrander, Milan S. Geybels, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Rasmus Bisbjerg, Martin Andreas Røder, Peter Iversen, Hermann Brenner, Katarina Cuk, Bernd Holleczek, Christiane Maier, Manuel Luedeke, Thomas Schnoeller, Jeri Kim, Christopher J. Logothetis, Esther M. John, Manuel R. Teixeira, Paula Paulo, Marta Cardoso, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, Kim De Ruyck, Gert De Meerleer, Piet Ost, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Daniel W. Lin, Lisa F. Newcomb, Davor Lessel, Marija Gamulin, Tomislav Kulis, Radka Kaneva, Nawaid Usmani, Sandeep Singhal, Chavdar Slavov, Vanio Mitev, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Monique J. Roobol, Guido Jenster, Ron H. N. van Schaik, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Jianfeng Xu, Kay-Tee Khaw, Lisa Cannon-Albright, Hardev Pandha, Agnieszka Michael, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Sara Lindstrom, Constance Turman, Jing Ma, David J. Hunter, Elio Riboli, Afshan Siddiq, Federico Canzian, Laurence N. Kolonel, Loic Le Marchand, Robert N. Hoover, Mitchell J. Machiela, Zuxi Cui, Peter Kraft, Christopher I. Amos, David V. Conti, Douglas F. Easton, Fredrik Wiklund, Stephen J. Chanock, Brian E. Henderson, Zsofia Kote-Jarai, Christopher A. Haiman, Rosalind A. Eeles

ABSTRACT

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. More... »

PAGES

928-936

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    7

    VOLUME

    50

    Author Affiliations

  • University Hospitals of Cleveland
  • University of Cambridge
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • Institute of Cancer Research
  • University of Southern California
  • University of Warwick
  • American Cancer Society
  • Fred Hutchinson Cancer Research Center
  • Translational Research Institute
  • Cancer Council Queensland
  • Garvan Institute of Medical Research
  • University of Adelaide
  • Peter MacCallum Cancer Centre
  • Karolinska Institute
  • University College London
  • Turku University Hospital
  • University of Tampere
  • University of Turku
  • Uppsala University
  • University of Manchester
  • Harvard University
  • Washington University in St. Louis
  • Tenon Hospital
  • Aarhus University
  • Aarhus University Hospital
  • Oslo University Hospital
  • University of Oxford
  • University of Bristol
  • Princess Margaret Cancer Centre
  • Icahn School of Medicine at Mount Sinai
  • University of Rochester Medical Center
  • Albert Einstein College of Medicine
  • Queen Mary University of London
  • Second Military Medical University
  • Nanjing Medical University
  • Chongqing Medical University
  • Zhongshan Hospital
  • Liaoning Provincial People's Hospital
  • University of Melbourne
  • Monash University
  • University of Tasmania
  • Brigham and Women's Hospital
  • Complejo Hospitalario Universitario de Santiago
  • Pompeu Fabra University
  • University of Cantabria
  • Moffitt Cancer Center
  • Louisiana State University Health Sciences Center New Orleans
  • University of Washington
  • Pomeranian Medical University
  • National Human Genome Research Institute
  • University of Copenhagen
  • German Cancer Research Center
  • Krebsregister Saarland
  • University Hospital Ulm
  • The University of Texas MD Anderson Cancer Center
  • Stanford University
  • University of Porto
  • City Of Hope National Medical Center
  • Ghent University
  • Ghent University Hospital
  • University of Malaya
  • Subang Jaya Medical Centre
  • University Medical Center Hamburg-Eppendorf
  • University Hospital Centre Zagreb
  • Medical University of Sofia
  • University of Alberta
  • KU Leuven
  • Universitaire Ziekenhuizen Leuven
  • University of Surrey
  • University of California, San Diego
  • University Hospital Complex Of Vigo
  • Erasmus University Medical Center
  • University of Paris-Sud
  • NorthShore University HealthSystem
  • George E. Wahlen Department of VA Medical Center
  • Mayo Clinic
  • Imperial College London
  • University of Hawaii at Manoa
  • Case Western Reserve University
  • Dartmouth–Hitchcock Medical Center
  • Royal Marsden NHS Foundation Trust
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0142-8

    DOI

    http://dx.doi.org/10.1038/s41588-018-0142-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1104478461

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29892016


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