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A genome-wide association study of prostate cancer in West African men |
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| Authors: | Michael Blaise Cook Zhaoming Wang Edward D Yeboah Yao Tettey Richard B Biritwum Andrew A Adjei Evelyn Tay Ann Truelove Shelley Niwa Charles C Chung Annand P Chokkalingam Lisa W Chu Meredith Yeager Amy Hutchinson Kai Yu Kristin A Rand Christopher A Haiman Robert N Hoover Ann W Hsing Stephen J Chanock |
| Institution: | 1. 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 2. Cancer Genomics Research Laboratory, NCI-DCEG, SAIC-Frederick Inc, Frederick, MD, USA 3. Korle Bu Teaching Hospital, PO Box 77, Accra, Ghana 4. University of Ghana Medical School, PO Box 4236, Accra, Ghana 5. Westat, 1600 Research Boulevard, Rockville, MD, 20850-3129, USA 6. School of Public Health, University of California, Berkeley, CA, USA 7. Cancer Prevention Institute of California, 2201 Walnut Avenue, Suite 300, Fremont, CA, 94538, USA 8. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA 9. Stanford Cancer Institute, Stanford University, 875 Blake Wilbur Drive Stanford, Stanford, CA, 94305, USA |
| 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. |
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