Department of Clinical Laboratory, The Third Affiliated Hospital of Nanjing Medical University, Yizheng, China.
Mol Carcinog. 2012 Oct;51 Suppl 1:E183-90. doi: 10.1002/mc.21914. Epub 2012 May 16.
The DNA repair gene Ku70 plays a key role in the DNA double strand break (DSB) repair system. Defects in DSB repair capacity can lead to genomic instability. We hypothesized that the Ku70 C-1310G polymorphism (rs2267437) was associated with risk of renal cell carcinoma (RCC). We genotyped the Ku70 C-1310G polymorphism in a case-control study of 620 patients and 623 controls in a Chinese population and assessed the effects of C-1310G polymorphism on RCC susceptibility and survival. We then examined the functionality of this polymorphism. Compared with the Ku70-1310CC genotype, the CG and CG/GG genotypes had a significantly increased risk of RCC [adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.16-1.87 for CG and OR = 1.47, 95% CI = 1.16-1.86 for CG/GG]. However, the C-1310G polymorphism did not influence the survival of RCC. The in vivo experiments with normal renal tissues revealed statistically significantly lower Ku70 mRNA expression in samples with CG/GG genotypes relative to those with the CC genotype (P < 0.05). In vitro luciferase assays in various cell lines showed lower luciferase activity for the -1310G allele than for the -1310C allele. These results suggest that the Ku70 C-1310G polymorphism is involved in the etiology of RCC and thus may be a marker for genetic susceptibility to RCC in Chinese populations. Larger studies are warranted to validate our findings.
DNA 修复基因 Ku70 在 DNA 双链断裂 (DSB) 修复系统中发挥着关键作用。DSB 修复能力的缺陷可导致基因组不稳定。我们假设 Ku70 C-1310G 多态性 (rs2267437) 与肾细胞癌 (RCC) 的风险相关。我们在中国人群的病例对照研究中对 620 例患者和 623 例对照进行了 Ku70 C-1310G 多态性的基因分型，并评估了 C-1310G 多态性对 RCC 易感性和生存的影响。然后，我们研究了该多态性的功能。与 Ku70-1310CC 基因型相比，CG 和 CG/GG 基因型的 RCC 风险显著增加[调整后的比值比 (OR) = 1.47，95%置信区间 (CI) = 1.16-1.87 对于 CG 和 OR = 1.47，95%CI = 1.16-1.86 对于 CG/GG]。然而，C-1310G 多态性并不影响 RCC 的生存。正常肾组织的体内实验表明，与 CC 基因型相比，CG/GG 基因型的 Ku70 mRNA 表达显著降低 (P < 0.05)。在各种细胞系中的体外荧光素酶实验表明，-1310G 等位基因的荧光素酶活性低于-1310C 等位基因。这些结果表明，Ku70 C-1310G 多态性参与了 RCC 的发病机制，因此可能是中国人群 RCC 遗传易感性的标志物。需要更大的研究来验证我们的发现。
