Prostate Cancer Susceptibility in Men of African Ancestry at 8q24
Recommended Citation
Han Y, Rand KA, Hazelett DJ, Ingles SA, Kittles RA, Strom SS, Rybicki BA, Nemesure B, Isaacs WB, Stanford JL, Zheng W, Schumacher FR, Berndt SI, Wang Z, Xu J, Rohland N, Reich D, Tandon A, Pasaniuc B, Allen A, Quinque D, Mallick S, Notani D, Rosenfeld MG, Jayani RS, Kolb S, Gapstur SM, Stevens VL, Pettaway CA, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, John EM, Murphy AB, Signorello LB, Carpten J, Leske MC, Wu SY, Hennis AJ, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Witte JS, Casey G, Lubwama A, Pooler LC, Sheng X, Coetzee GA, Cook MB, Chanock SJ, Stram DO, Watya S, Blot WJ, Conti DV, Henderson BE, and Haiman CA. Prostate cancer susceptibility in men of African ancestry at 8q24. J Natl Cancer Inst 2016; 108(7).
Document Type
Article
Publication Date
7-1-2016
Publication Title
Journal of the National Cancer Institute
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.
Medical Subject Headings
Black or African American; Aged; Aged, 80 and over; Case-Control Studies; Chromosomes, Human, Pair 8; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prostatic Neoplasms; RNA, Long Noncoding; United States
PubMed ID
26823525
Volume
108
Issue
7
