8q24 risk alleles in West African and Caribbean men

作者:Murphy Adam B; Ukoli Flora; Freeman Vincent; Bennett Frankly; Aiken William; Tulloch Trevor; Coard Kathleen; Angwafo Fru; Kittles Rick A*
来源:Prostate, 2012, 72(12): 1366-1373.
DOI:10.1002/pros.22486

摘要

BACKGROUND Multiple genetic studies have confirmed associations of 8q24 variants with susceptibility to prostate cancer (CaP). However, the magnitude of risk conferred in men living in West Africa is unknown. METHODS Here we determine the prevalence of 8q24 risk alleles and test for association with CaP risk alleles in West African (WA) descent populations from rural Nigeria, Cameroon, and the Caribbean island of Jamaica. Ten 8q24 SNPs were genotyped in histologically confirmed CaP cases (n?=?308) and clinically evaluated controls (n?=?469). In addition, unrelated individuals from Sierra Leone (n?=?380) were genotyped for comparison of allele frequency comparisons. RESULTS SNPs rs6983561, rs7008482, and rs16901979 were significantly associated with CaP risk in WAs (P?<?0.03). No associations with CaP were observed in our Caribbean samples. Risk alleles for rs6983267, rs7008482, and rs7000448 were highly prevalent (>84%) in West Africa. We also reveal that the A-risk allele for the African-specific SNP bd11934905 was not observed in 1,886 chromosomes from three WA ethnic groups suggesting that this allele may not be common across West Africa, but is geographically restricted to specific ethnic group(s). CONCLUSIONS We provide evidence of association of 8q24 SNPs with prostate cancer risk in men from Nigeria and Cameroon. Our study is the first to reveal genetic risk due to 8q24 variants (in particular, region 2) with CaP within two WA countries. Most importantly, in light of the disparate burden of CaP in African-Americans, our findings support the need for larger genetic studies in WA descent populations to validate and discern function of susceptibility loci in the 8q24 region. Prostate 72:13661373, 2012.

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