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

J Natl Cancer Inst
Authors
Keywords
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.

Year of Publication
2016
Journal
J Natl Cancer Inst
Volume
108
Issue
7
Date Published
2016 Jul
ISSN
1460-2105
DOI
10.1093/jnci/djv431
PubMed ID
26823525
PubMed Central ID
PMC4948565
Links
Grant list
CA54281 / CA / NCI NIH HHS / United States
ES007784 / ES / NIEHS NIH HHS / United States
1U58DP000807-03 / DP / NCCDPHP CDC HHS / United States
CA88164 / CA / NCI NIH HHS / United States
CA127298 / CA / NCI NIH HHS / United States
CA092579 / CA / NCI NIH HHS / United States
U10 CA037429 / CA / NCI NIH HHS / United States
R01 CA136924 / CA / NCI NIH HHS / United States
CA1326792 / CA / NCI NIH HHS / United States
P50 CA140388 / CA / NCI NIH HHS / United States
5UM1CA182883 / CA / NCI NIH HHS / United States
N01-PC-35139 / PC / NCI NIH HHS / United States
UG1 CA189974 / CA / NCI NIH HHS / United States
CA056678 / CA / NCI NIH HHS / United States
CA37429 / CA / NCI NIH HHS / United States
HG004726 / HG / NHGRI NIH HHS / United States
CA68578 / CA / NCI NIH HHS / United States
CA63464 / CA / NCI NIH HHS / United States
CA082664 / CA / NCI NIH HHS / United States
CA148085 / CA / NCI NIH HHS / United States
CA140388 / CA / NCI NIH HHS / United States
CA092447 / CA / NCI NIH HHS / United States
CA68485 / CA / NCI NIH HHS / United States
UM1 CA182883 / CA / NCI NIH HHS / United States
CA165862 / CA / NCI NIH HHS / United States