Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL 60637, USA.
Prostate. 2010 Feb 15;70(3):270-5. doi: 10.1002/pros.21061.
Prostate cancer (Pca) is a common malignancy that disproportionately affects African American men (AA). Recently there have been several genome-wide association studies (GWAS) implicating new prostate cancer risk loci along chromosomes 2, 3, 6, 7, 8, 10, 11, 12, 17, 19, and X in populations of European ancestry. Given the higher incidence and mortality for AAs, and differences in allele frequencies and haplotype structures between African and European descent populations, it is important to assess the impact of these candidate risk loci in AAs.
Here we evaluated 20 single nucleotide polymorphisms (SNPs) associated with prostate cancer risk in recent GWAS studies, in AA prostate cancer cases and controls.
We replicated five of the SNPs in our AA population, rs10896449 on 11q13.2 (P = 0.009), rs2735839 on 19q33.33 region, (P = 0.04), rs443076 on chromosome 17q12 (P = 0.008), rs5945572 on Xp11.22 (P = 0.05), as well as the rare variant specific to west African ancestry, bd11934905 in region 2 of 8q24 (P = 1 x 10(-4)).
While we were able to replicate a few of the previous GWAS SNPs, we were not able to confirm the vast majority of these associations in our AA population. This finding further supports the need to perform GWAS and additional fine mapping in AAs to locate additional susceptibility loci.
前列腺癌(Pca)是一种常见的恶性肿瘤,不成比例地影响非裔美国男性(AA)。最近,有几项全基因组关联研究(GWAS)表明,在欧洲血统人群中,染色体 2、3、6、7、8、10、11、12、17、19 和 X 上存在新的前列腺癌风险位点。鉴于 AA 的发病率和死亡率较高,以及非洲和欧洲血统人群之间的等位基因频率和单倍型结构差异,评估这些候选风险位点在 AA 中的影响非常重要。
在这里,我们评估了最近 GWAS 研究中与前列腺癌风险相关的 20 个单核苷酸多态性(SNP)在 AA 前列腺癌病例和对照中的作用。
我们在 AA 人群中复制了其中的 5 个 SNP,11q13.2 上的 rs10896449(P = 0.009),19q33.33 区域上的 rs2735839(P = 0.04),17q12 上的 rs443076(P = 0.008),Xp11.22 上的 rs5945572(P = 0.05),以及特属于西非血统的罕见变异体 rs5945572(P = 0.05)。
虽然我们能够复制以前 GWAS 中的一些 SNP,但我们无法在 AA 人群中证实大多数这些关联。这一发现进一步支持了在 AA 中进行 GWAS 和额外的精细映射以定位额外的易感性位点的必要性。