A genome-wide association study of prostate cancer in West African men

• Published in: Human genetics Vol. 133; no. 5; pp. 509 - 521
• Main Authors: Cook, Michael Blaise, Wang, Zhaoming, Yeboah, Edward D., Tettey, Yao, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Chung, Charles C., Chokkalingam, Annand P., Chu, Lisa W., Yeager, Meredith, Hutchinson, Amy, Yu, Kai, Rand, Kristin A., Haiman, Christopher A., Hoover, Robert N., Hsing, Ann W., Chanock, Stephen J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2014; Springer; Springer Nature B.V
• Subjects: Africa, Western; African Americans; Age; Aged; Analysis; Biomedical and Life Sciences; Biomedicine; Cancer; Consortia; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetic research; Genome-Wide Association Study; Genomes; Genomics; Health aspects; Health care; Human Genetics; Humans; International comparisons; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Mortality; Oncology, Experimental; Original Investigation; Preventive medicine; Prostate cancer; Prostatic Neoplasms - genetics; Teaching hospitals; Africa, Western; Ghana; California; United States > US; West Africa; Accra Ghana; Prostate Cancer Locus; Prostate Cancer; Gleason Score; Single Nucleotide Polymorphism; Prostate Cancer Case
• ISSN: 0340-6717; 1432-1203; 1432-1203
• DOI: 10.1007/s00439-013-1387-z

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.