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


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.

SUBMITTER: Conti DV 

PROVIDER: S-EPMC5448553 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Conti David V DV   Wang Kan K   Sheng Xin X   Bensen Jeannette T JT   Hazelett Dennis J DJ   Cook Michael B MB   Ingles Sue A SA   Kittles Rick A RA   Strom Sara S SS   Rybicki Benjamin A BA   Nemesure Barbara B   Isaacs William B WB   Stanford Janet L JL   Zheng Wei W   Sanderson Maureen M   John Esther M EM   Park Jong Y JY   Xu Jianfeng J   Stevens Victoria L VL   Berndt Sonja I SI   Huff Chad D CD   Wang Zhaoming Z   Yeboah Edward D ED   Tettey Yao Y   Biritwum Richard B RB   Adjei Andrew A AA   Tay Evelyn E   Truelove Ann A   Niwa Shelley S   Sellers Thomas A TA   Yamoah Kosj K   Murphy Adam B AB   Crawford Dana C DC   Gapstur Susan M SM   Bush William S WS   Aldrich Melinda C MC   Cussenot Olivier O   Petrovics Gyorgy G   Cullen Jennifer J   Neslund-Dudas Christine C   Stern Mariana C MC   Jarai Zsofia-Kote ZK   Govindasami Koveela K   Chokkalingam Anand P AP   Hsing Ann W AW   Goodman Phyllis J PJ   Hoffmann Thomas T   Drake Bettina F BF   Hu Jennifer J JJ   Clark Peter E PE   Van Den Eeden Stephen K SK   Blanchet Pascal P   Fowke Jay H JH   Casey Graham G   Hennis Anselm J M AJM   Han Ying Y   Lubwama Alexander A   Thompson Ian M IM   Leach Robin R   Easton Douglas F DF   Schumacher Fredrick F   Van den Berg David J DJ   Gundell Susan M SM   Stram Alex A   Wan Peggy P   Xia Lucy L   Pooler Loreall C LC   Mohler James L JL   Fontham Elizabeth T H ETH   Smith Gary J GJ   Taylor Jack A JA   Srivastava Shiv S   Eeles Rosalind A RA   Carpten John J   Kibel Adam S AS   Multigner Luc L   Parent Marie-Elise ME   Menegaux Florence F   Cancel-Tassin Geraldine G   Klein Eric A EA   Brureau Laurent L   Stram Daniel O DO   Watya Stephen S   Chanock Stephen J SJ   Witte John S JS   Blot William J WJ   Henderson Brian E BE   Haiman Christopher A CA  

Journal of the National Cancer Institute 20170801 8


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  ...[more]

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