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

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.

Adjei AA, Aldrich MC, Bensen JT, Berndt SI, Biritwum RB, Blanchet P, Blot WJ, Brureau L, Bush WS, Cancel-Tassin G, Carpten J, Casey G, Chanock SJ, Chokkalingam AP, Clark PE, Conti DV, Cook MB, Crawford DC, Cullen J, Cussenot O, Drake BF, Easton DF, Eeles RA, Fontham ETH, Fowke JH, Gapstur SM, Goodman PJ, Govindasami K, Gundell SM, Haiman CA, Han Y, Hazelett DJ, Henderson BE, Hennis AJM, Hoffmann T, Hsing AW, Hu JJ, Huff CD, Ingles SA, Isaacs WB, Jarai ZK, John EM, Kibel AS, Kittles RA, Klein EA, Leach R, Lubwama A, Menegaux F, Mohler JL, Multigner L, Murphy AB, Nemesure B, Neslund-Dudas C, Niwa S, Parent ME, Park JY, Petrovics G, Pooler LC, Rybicki BA, Sanderson M, Schumacher F, Sellers TA, Sheng X, Smith GJ, Srivastava S, Stanford JL, Stern MC, Stevens VL, Stram A, Stram DO, Strom SS, Tay E, Taylor JA, Tettey Y, Thompson IM, Truelove A, Van Den Eeden SK, Van den Berg DJ, Wan P, Wang K, Wang Z, Watya S, Witte JS, Xia L, Xu J, Yamoah K, Yeboah ED, Zheng W


J. Natl. Cancer Inst., 2017, 109 (8)

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