Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Prostate. 2012 Sep 1;72(12):1366-73. doi: 10.1002/pros.22486. Epub 2012 Jan 10.
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.
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.
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).
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.
多项遗传研究证实,8q24 变异与前列腺癌(CaP)易感性有关。然而,居住在西非的男性所面临的风险程度尚不清楚。
本研究旨在确定西非(WA)血统人群中 8q24 风险等位基因的流行率,并检测其与来自尼日利亚农村、喀麦隆和牙买加加勒比海岛屿的 CA 患者风险等位基因的相关性。在经组织学证实的 CaP 病例(n=308)和临床评估对照(n=469)中,对 10 个 8q24 SNPs 进行了基因分型。此外,还对来自塞拉利昂的无关个体(n=380)进行了基因分型,以比较等位基因频率的比较。
rs6983561、rs7008482 和 rs16901979 与 WA 人群的 CaP 风险显著相关(P<0.03)。在我们的加勒比样本中,未观察到与 CaP 相关的 SNPs。rs6983267、rs7008482 和 rs7000448 的风险等位基因在西非的流行率很高(>84%)。我们还发现,在来自三个 WA 族裔的 1886 条染色体中,bd11934905 的 A 风险等位基因并未被观察到,这表明该等位基因可能不是整个西非普遍存在的,而是在地理上局限于特定的族裔群体。
本研究提供了 rs6983561、rs7008482 和 rs16901979 与尼日利亚和喀麦隆男性前列腺癌风险相关的证据。本研究首次揭示了 8q24 变异(特别是 2 区)与两个 WA 国家 CaP 之间的遗传风险。最重要的是,鉴于非洲裔美国人患 CaP 的负担差异很大,我们的研究结果支持在 WA 血统人群中进行更大规模的遗传研究,以验证和区分 8q24 区域易感性基因座的功能。