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.
Written by:
Wang W, Pan X, Huo X, Yan F, Wang M, Wang D, Gao Y, Cao Q, Luo D, Qin C, Yin C, Zhang Z. Are you the author?
Department of Clinical Laboratory, The Third Affiliated Hospital of Nanjing Medical University, Yizheng, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; Department of Molecular & Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Reference: Mol Carcinog. 2012 Oct;51 Suppl 1:E183-90.
doi: 10.1002/mc.21914
PubMed Abstract
PMID: 22593040
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