Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Prostate. 2011 Jun 1;71(8):881-91. doi: 10.1002/pros.21304. Epub 2010 Nov 17.
Genome-wide association studies (GWAS) have identified numerous common SNPs associated with prostate cancer (CaP) risk in men of European descent. This study evaluates GWAS SNPs associated with CaP in African Americans (AAs) and European Americans (EA).
Eight hundred SNPs were genotyped, including 32 from European-based GWAS and 35 flanking SNPs, in 417 AA and 455 EA cases from the NC-LA Prostate Cancer Project (PCaP) and compared to 925 AA and 1,687 EA controls from Illumina's iControlDB. The 32 GWAS SNPs were evaluated for their predictive power to discriminate between cases and controls using ROC curves.
Of the 32 GWAS SNPs, 13 were significant at P < 0.05 in EA and 4 in AA (rs6983267, rs7017300, rs1859962, rs6501455). Three of 35 flanking SNPs, all from chromosome 8q, reached study-wide significance (P < 3.5 × 10(-5)); 2 in AA (rs10505476 rs6985504) and 1 in EA (rs16901970). Among the remaining 656 SNPs, 2 were associated with CaP (P < 3.5 × 10(-5)): rs1472606 (OR: 1.43 in EA) and rs9351265 (OR: 1.48 in AA) both in intergenic regions. For the 32 GWAS SNPs, ROC plots yielded AUC estimates too low for clinical use (EA AUC = 0.60 and AA AUC = 0.56).
This study confirms a large proportion of CaP associated regions implicated by European-based GWAS and provides evidence that some regions may be important in AA CaP risk. Despite the identification of a large panel of GWAS replicated SNPs for CaP, this panel is not appropriate for clinical screening.
全基因组关联研究（GWAS）已经确定了许多与欧洲裔男性前列腺癌（CaP）风险相关的常见 SNP。本研究评估了与非裔美国人和欧洲裔美国人（EA）的 CaP 相关的 GWAS SNP。
在 NC-LA 前列腺癌项目（PCaP）中，对 417 名 AA 和 455 名 EA 病例和 925 名 AA 和 1687 名 EA 对照进行了 800 个 SNP 的基因分型，包括 32 个基于欧洲的 GWAS SNP 和 35 个侧翼 SNP。使用 ROC 曲线评估这 32 个 GWAS SNP 区分病例和对照的预测能力。
在 EA 中，有 13 个 GWAS SNP 达到了 P < 0.05 的显著性水平，而在 AA 中则有 4 个（rs6983267、rs7017300、rs1859962、rs6501455）。35 个侧翼 SNP 中有 3 个达到了全研究范围的显著性水平（P < 3.5×10(-5)）；2 个在 AA 中（rs10505476 rs6985504），1 个在 EA 中（rs16901970）。在其余的 656 个 SNP 中，有 2 个与 CaP 相关（P < 3.5×10(-5)）：rs1472606（OR：EA 中的 1.43）和 rs9351265（OR：AA 中的 1.48），都位于基因间区域。对于 32 个 GWAS SNP，ROC 图的 AUC 估计值太低，不适合临床使用（EA AUC = 0.60，AA AUC = 0.56）。
本研究证实了欧洲 GWAS 所涉及的 CaP 相关区域的很大一部分，并提供了一些证据表明，某些区域可能对 AA CaP 风险很重要。尽管已经确定了大量用于 CaP 的 GWAS 复制 SNP，但该面板不适合临床筛查。
