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中国男性前列腺癌风险相关单核苷酸多态性的系统验证研究。

Systematic confirmation study of reported prostate cancer risk-associated single nucleotide polymorphisms in Chinese men.

机构信息

Fudan-VARI Center for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China.

出版信息

Cancer Sci. 2011 Oct;102(10):1916-20. doi: 10.1111/j.1349-7006.2011.02036.x. Epub 2011 Aug 10.

Abstract

More than 30 prostate cancer (PCa) risk-associated loci have been identified in populations of European descent by genome-wide association studies. We hypothesized that a subset of these loci might be associated with PCa risk in Chinese men. To test this hypothesis, 33 single nucleotide polymorphisms (SNP), one each from the 33 independent PCa risk-associated loci reported in populations of European descent, were investigated for their associations with PCa risk in a case-control study of Chinese men (1108 cases and 1525 controls). We found that 11 of the 33 SNP were significantly associated with PCa risk in Chinese men (P < 0.05). The reported risk alleles were associated with increased risk for PCa, with allelic odds ratios ranging from 1.12 to 1.44. The most significant locus was located on 8q24 region 2 (rs16901979, P = 5.14 × 10(-9)) with a genome-wide significance (P < (-8) ), and three loci reached the Bonferroni correction significance level (P < 1.52 × 10(-3)), including 8q24 region 1 (rs1447295, P = 7.04 × 10(-6)), 8q24 region 5 (rs10086908, P = 9.24 × 10(-4)) and 8p21 (rs1512268, P = 9.39 × 10(-4)). Our results suggest that a subset of the PCa risk-associated SNP discovered by genome-wide association studies among men of European descent is also associated with PCa risk in Chinese men. This finding provides evidence of ethnic differences and similarity in genetic susceptibility to PCa. Genome-wide association studies in Chinese men are needed to identify Chinese-specific PCa risk-associated SNP.

摘要

已有超过 30 个前列腺癌(PCa)风险相关基因座在欧洲裔人群中通过全基因组关联研究(GWAS)被鉴定出来。我们假设其中一些基因座可能与中国男性的 PCa 风险相关。为了验证这一假设,我们在中国男性的病例对照研究中(1108 例病例和 1525 例对照),针对来自欧洲裔人群中报告的 33 个独立的 PCa 风险相关基因座中的每一个基因座,检测了 33 个单核苷酸多态性(SNP)与 PCa 风险的相关性。我们发现,这 33 个 SNP 中有 11 个与中国男性的 PCa 风险显著相关(P<0.05)。报道的风险等位基因与 PCa 风险增加相关,等位基因比值比(ORs)范围为 1.12 至 1.44。最显著的基因座位于 8q24 区域 2(rs16901979,P=5.14×10(-9)),具有全基因组显著性(P<(-8)),三个基因座达到了 Bonferroni 校正显著性水平(P<1.52×10(-3)),包括 8q24 区域 1(rs1447295,P=7.04×10(-6))、8q24 区域 5(rs10086908,P=9.24×10(-4))和 8p21(rs1512268,P=9.39×10(-4))。我们的结果表明,在欧洲裔男性中通过全基因组关联研究发现的 PCa 风险相关 SNP 中的一部分也与中国男性的 PCa 风险相关。这一发现提供了遗传易感性在种族差异和相似性方面的证据。需要在中国男性中进行全基因组关联研究,以确定中国特有的 PCa 风险相关 SNP。

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