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Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry.

  • Author(s): Conti, David V;
  • Wang, Kan;
  • Sheng, Xin;
  • Bensen, Jeannette T;
  • Hazelett, Dennis J;
  • Cook, Michael B;
  • Ingles, Sue A;
  • Kittles, Rick A;
  • Strom, Sara S;
  • Rybicki, Benjamin A;
  • Nemesure, Barbara;
  • Isaacs, William B;
  • Stanford, Janet L;
  • Zheng, Wei;
  • Sanderson, Maureen;
  • John, Esther M;
  • Park, Jong Y;
  • Xu, Jianfeng;
  • Stevens, Victoria L;
  • Berndt, Sonja I;
  • Huff, Chad D;
  • Wang, Zhaoming;
  • Yeboah, Edward D;
  • Tettey, Yao;
  • Biritwum, Richard B;
  • Adjei, Andrew A;
  • Tay, Evelyn;
  • Truelove, Ann;
  • Niwa, Shelley;
  • Sellers, Thomas A;
  • Yamoah, Kosj;
  • Murphy, Adam B;
  • Crawford, Dana C;
  • Gapstur, Susan M;
  • Bush, William S;
  • Aldrich, Melinda C;
  • Cussenot, Olivier;
  • Petrovics, Gyorgy;
  • Cullen, Jennifer;
  • Neslund-Dudas, Christine;
  • Stern, Mariana C;
  • Jarai, Zsofia-Kote;
  • Govindasami, Koveela;
  • Chokkalingam, Anand P;
  • Hsing, Ann W;
  • Goodman, Phyllis J;
  • Hoffmann, Thomas;
  • Drake, Bettina F;
  • Hu, Jennifer J;
  • Clark, Peter E;
  • Van Den Eeden, Stephen K;
  • Blanchet, Pascal;
  • Fowke, Jay H;
  • Casey, Graham;
  • Hennis, Anselm JM;
  • Han, Ying;
  • Lubwama, Alexander;
  • Thompson, Ian M;
  • Leach, Robin;
  • Easton, Douglas F;
  • Schumacher, Fredrick;
  • Van den Berg, David J;
  • Gundell, Susan M;
  • Stram, Alex;
  • Wan, Peggy;
  • Xia, Lucy;
  • Pooler, Loreall C;
  • Mohler, James L;
  • Fontham, Elizabeth TH;
  • Smith, Gary J;
  • Taylor, Jack A;
  • Srivastava, Shiv;
  • Eeles, Rosalind A;
  • Carpten, John;
  • Kibel, Adam S;
  • Multigner, Luc;
  • Parent, Marie-Elise;
  • Menegaux, Florence;
  • Cancel-Tassin, Geraldine;
  • Klein, Eric A;
  • Brureau, Laurent;
  • Stram, Daniel O;
  • Watya, Stephen;
  • Chanock, Stephen J;
  • Witte, John S;
  • Blot, William J;
  • Henderson, Brian E;
  • Haiman, Christopher A;
  • PRACTICAL/ELLIPSE Consortium
  • et al.
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.

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