title: A genome-wide association study of prostate cancer in West African men.
abstract: Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 9609 Medical Center Drive, Rm 7-E106, MSC 9774, Bethesda, MD, 20892-9774, USA, cookmich@mail.nih.gov.
authors.forename: Michael Blaise
authors.initials: MB
authors.lastname: Cook
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Edward D
authors.initials: ED
authors.lastname: Yeboah
authors.forename: Yao
authors.initials: Y
authors.lastname: Tettey
authors.forename: Richard B
authors.initials: RB
authors.lastname: Biritwum
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Adjei
authors.forename: Evelyn
authors.initials: E
authors.lastname: Tay
authors.forename: Ann
authors.initials: A
authors.lastname: Truelove
authors.forename: Shelley
authors.initials: S
authors.lastname: Niwa
authors.forename: Charles C
authors.initials: CC
authors.lastname: Chung
authors.forename: Annand P
authors.initials: AP
authors.lastname: Chokkalingam
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Chu
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Rand
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
mesh_terms: D000354:Africa, Western; D000368:Aged; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics*