Genetic Risk of Prostate Cancer in Ugandan Men

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dc.contributor.authorDu, Zhaohui
dc.contributor.authorLubmawa, Alexander
dc.contributor.authorGundell, Susan
dc.contributor.authorWan, Peggy
dc.contributor.authorNalukenge, Cissy
dc.contributor.authorMuwanga, Proscovia
dc.contributor.authorLutalo, Moses
dc.contributor.authorNansereko, Deborah
dc.contributor.authorNdaruhutse, Olivia
dc.contributor.authorKatuku, Molly
dc.contributor.authorNassanga, Rosemary
dc.contributor.authorAfrican Ancestry Prostate Cancer Consortium
dc.contributor.authorAsiimwe, Frank
dc.contributor.authorMasaba, Benon
dc.contributor.authorKaggwa, Sam
dc.contributor.authorNamuguzi, Dan
dc.contributor.authorKiddu, Vicky
dc.contributor.authorMutema, George
dc.contributor.authorConti, David V.
dc.contributor.authorLuke, Asiimwe
dc.contributor.authorJob, Kuteesa
dc.contributor.authorHenry, Dabanja M.
dc.contributor.authorHaiman, Christopher A.
dc.contributor.authorWatya, Stephen
dc.date.accessioned2022-03-20T19:59:18Z
dc.date.available2022-03-20T19:59:18Z
dc.date.issued2018
dc.description.abstractMen of African-ancestry have elevated prostate cancer (PCa) incidence and mortality compared to men of other racial groups. There is support for a genetic contribution to this disparity, with evidence of genetic heterogeneity in the underlying risk alleles between populations. Studies of PCa among African men may inform the contribution of genetic risk factors to the elevated disease burden in this population.We conducted an association study of >100 previously reported PCa risk alleles among 571 incidence cases and 485 controls among Uganda men. Unconditional logistic regression was used to test genetic associations and a polygenic risk score (PRS) was derived to assess the cumulative effect of the known risk alleles in association with PCa risk. In an exploratory analysis, we also tested associations of 17 125 421 genotyped and imputed markers genome-wide in association with PCa risk.Of the 111 known risk loci with a frequency >1%, 75 (68%) had effects that were directionally consistent with the initial discovery population,14 (13%) of which were nominally significantly associated with PCa risk at P < 0.05. Compared to men with average risk (25th−75th percentile in PRS distribution), Ugandan men in the top 10% of the PRS, constructed of alleles outside of 8q24, had a 2.9-fold (95%CI: 1.75, 4.97) risk of developing PCa; risk for the top 10% increased to 4.86 (95%CI: 2.70, 8.76) with the inclusion of risk alleles at 8q24. In genome-wide association testing, the strongest associations were noted with known risk alleles located in the 8q24 region, including rs72725854 (OR = 3.37, P = 2.14 × 10−11) that is limited to populations of African ancestry (6% frequency).The ~100 known PCa risk variants were shown to effectively stratify PCa risk in Ugandan men, with 10% of men having a >4-fold increase in risk. The 8q24 risk region was also found to be a major contributor to PCa risk in Ugandan men, with the African ancestry-specific risk variant rs72725854 estimated to account for 12% of PCa in this population.en_US
dc.identifier.citationDu, Z., Lubmawa, A., Gundell, S., Wan, P., Nalukenge, C., Muwanga, P., Lutalo, M., Nansereko, D., Ndaruhutse, O., Katuku, M., Nassanga, R., African Ancestry Prostate Cancer Consortium (AAPC), Asiimwe, F., Masaba, B., Kaggwa, S., Namuguzi, D., Kiddu, V., Mutema, G., Conti, D. V., Luke, A., … Watya, S. (2018). Genetic risk of prostate cancer in Ugandan men. The Prostate, 78(5), 370–376. https://doi.org/10.1002/pros.23481en_US
dc.identifier.urihttps://nru.uncst.go.ug/xmlui/handle/123456789/2833
dc.language.isoenen_US
dc.publisherThe Prostateen_US
dc.subject8q24, African men, GWAS, prostate canceren_US
dc.titleGenetic Risk of Prostate Cancer in Ugandan Menen_US
dc.typeArticleen_US
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