Year: 2017
Type: article
Study design: Observational Study
Abstract: Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.
DOI: 10.1093/jnci/djx084
Authors: David V Conti, Kan Wang, Xin Sheng, Jeannette T Bensen, Dennis J Hazelett, Michael B Cook, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, Barbara Nemesure, William B Isaacs, Janet L Stanford, Wei Zheng, Maureen Sanderson, Esther M John, Jong Y Park, Jianfeng Xu, Victoria L Stevens, Sonja I Berndt, Chad D Huff, Zhaoming Wang, Edward D Yeboah, Yao Tettey, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A Sellers, Kosj Yamoah, Adam B Murphy, Dana C Crawford, Susan M Gapstur, William S Bush, Melinda C Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine Neslund-Dudas, Mariana C Stern, Zsofia-Kote Jarai, Koveela Govindasami, Anand P Chokkalingam, Ann W Hsing, Phyllis J Goodman, Thomas Hoffmann, Bettina F Drake, Jennifer J Hu, Peter E Clark, Stephen K Van Den Eeden, Pascal Blanchet, Jay H Fowke, Graham Casey, Anselm J. M Hennis, Ying Han, Alexander Lubwama, Ian M. Thompson, Robin Leach, Douglas F Easton, Fredrick Schumacher, David J Van den Berg, Susan M Gundell, Alex Stram, Peggy Wan, Lucy Xia, Loreall C Pooler, James L Mohler, Elizabeth T. H Fontham, Gary J Smith, Jack A Taylor, Shiv Srivastava, Rosalind A Eeles, John Carpten, Adam S Kibel, Luc Multigner, Marie-Elise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A Klein, Laurent Brureau, Daniel O Stram, Stephen Watya, Stephen J Chanock, John S Witte, William J Blot, Brian E Henderson, Christopher A Haiman
Institutions: University of Southern California, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Cedars-Sinai Medical Center, National Institutes of Health, Division of Cancer Epidemiology and Genetics, USC Norris Comprehensive Cancer Center, University of Arizona, University of Arizona Cancer Center, The University of Texas MD Anderson Cancer Center, Henry Ford Health, Henry Ford Hospital, Stony Brook University, Johns Hopkins University, Johns Hopkins Hospital, University of Washington, Fred Hutch Cancer Center, Vanderbilt University, Meharry Medical College, Stanford Medicine, Stanford Cancer Institute, Stanford University, Moffitt Cancer Center, Endeavor Health, American Cancer Society, St. Jude Children's Research Hospital, University of Ghana, Korle Bu Teaching Hospital, Westat (United States), Northwestern University, Case Western Reserve University, Vanderbilt University Medical Center, Université Pierre-et-Marie-Curie, Uniformed Services University of the Health Sciences, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, University of California, Berkeley, University of California, San Francisco, Washington University in St. Louis, University of Miami, Sylvester Comprehensive Cancer Center, Kaiser Permanente, Kaiser Permanente Northern California, Inserm, Institut de Recherche en Santé, Environnement et Travail, Centre Hospitalier Universitaire Pointe-à-Pitre, Université des Antilles, University of Virginia, University of the West Indies, Makerere University, The University of Texas at San Antonio Health Science Center, University of Cambridge, Roswell Park Comprehensive Cancer Center, Louisiana State University Health Sciences Center New Orleans, National Institute of Environmental Health Sciences, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center, Institut National de la Recherche Scientifique, Université du Québec, Université Paris-Sud, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Cleveland Clinic
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,436
Funders: Brigham and Women's Hospital, University of Southern California, Kaiser Permanente, Vanderbilt University, University of Miami, Northwestern University, Cleveland Clinic, University of Arizona Cancer Center, St. Jude Children's Research Hospital, University of Washington, Johns Hopkins University, Case Western Reserve University, Louisiana State University, Moffitt Cancer Center, Royal Marsden NHS Foundation Trust, NorthShore University HealthSystem, Institut national de la recherche scientifique, Cedars-Sinai Medical Center, Vanderbilt University Medical Center, Sylvester Comprehensive Cancer Center, University of Miami Health Systems, Cancer Research UK, Institut National de la Santé et de la Recherche Médicale, University of Ghana, Fakultet Medicinskih Nauka, Univerziteta U Kragujevcu, Stony Brook University, National Institutes of Health, School of Medicine, Stanford University, School of Medicine, Vanderbilt University, Uniformed Services University of the Health Sciences, University of Texas MD Anderson Cancer Center, University of North Carolina at Chapel Hill, University of California, San Francisco, University of Texas Health Science Center at San Antonio, Leonard M. Miller School of Medicine, National Cancer Institute, National Institute of Environmental Health Sciences, National Institute on Minority Health and Health Disparities, Stanford Cancer Institute, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Awards: G1017297203, G1740625458, G2505793412, PCPT and SELECT cohorts: Core Infrastructure Support for Cancer Research, Genetic Epidemiology of Prostate Cancer Risk and Progression, Elucidating Loci Involved in Prostate Cancer Suceptibility, G3828336601, G4141622387, G4192692896, G625482125, G697149933, Cancer Center Support Grant
OpenAlex ID: W2619186549