TY - JOUR
T1 - Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry
AU - for the PRACTICAL/ELLIPSE Consortium
AU - Conti, David V.
AU - Wang, Kan
AU - Sheng, Xin
AU - Bensen, Jeannette T.
AU - Hazelett, Dennis J.
AU - Cook, Michael B.
AU - Ingles, Sue A.
AU - Kittles, Rick A.
AU - Strom, Sara S.
AU - Rybicki, Benjamin A.
AU - Nemesure, Barbara
AU - Isaacs, William B.
AU - Stanford, Janet L.
AU - Zheng, Wei
AU - Sanderson, Maureen
AU - John, Esther M.
AU - Park, Jong Y.
AU - Xu, Jianfeng
AU - Stevens, Victoria L.
AU - Berndt, Sonja I.
AU - Haiman, Christopher A.
N1 - Publisher Copyright:
© 2017 The Author. Published by Oxford University Press.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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 cancerin men of African ancestry, we performed a genome-wide associationmeta-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 amissense 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.
AB - 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 cancerin men of African ancestry, we performed a genome-wide associationmeta-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 amissense 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.
UR - https://www.scopus.com/pages/publications/85021065500
U2 - 10.1093/jnci/djx084
DO - 10.1093/jnci/djx084
M3 - Article
C2 - 29117387
AN - SCOPUS:85021065500
SN - 0027-8874
VL - 109
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 8
ER -