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Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.


ABSTRACT: The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

SUBMITTER: Han Y 

PROVIDER: S-EPMC4948565 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.

Han Ying Y   Rand Kristin A KA   Hazelett Dennis J DJ   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   Schumacher Fredrick R FR   Berndt Sonja I SI   Wang Zhaoming Z   Xu Jianfeng J   Rohland Nadin N   Reich David D   Tandon Arti A   Pasaniuc Bogdan B   Allen Alex A   Quinque Dominique D   Mallick Swapan S   Notani Dimple D   Rosenfeld Michael G MG   Jayani Ranveer Singh RS   Kolb Suzanne S   Gapstur Susan M SM   Stevens Victoria L VL   Pettaway Curtis A CA   Yeboah Edward D ED   Tettey Yao Y   Biritwum Richard B RB   Adjei Andrew A AA   Tay Evelyn E   Truelove Ann A   Niwa Shelley S   Chokkalingam Anand P AP   John Esther M EM   Murphy Adam B AB   Signorello Lisa B LB   Carpten John J   Leske M Cristina MC   Wu Suh-Yuh SY   Hennis Anslem J M AJM   Neslund-Dudas Christine C   Hsing Ann W AW   Chu Lisa L   Goodman Phyllis J PJ   Klein Eric A EA   Zheng S Lilly SL   Witte John S JS   Casey Graham G   Lubwama Alex A   Pooler Loreall C LC   Sheng Xin X   Coetzee Gerhard A GA   Cook Michael B MB   Chanock Stephen J SJ   Stram Daniel O DO   Watya Stephen S   Blot William J WJ   Conti David V DV   Henderson Brian E BE   Haiman Christopher A CA  

Journal of the National Cancer Institute 20160127 7


The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Gh  ...[more]

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