title: A functional polymorphism C-1310G in the promoter region of Ku70/XRCC6 is associated with risk of renal cell carcinoma.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, The Third Affiliated Hospital of Nanjing Medical University, Yizheng, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xuping
authors.initials: X
authors.lastname: Pan
authors.forename: Xinying
authors.initials: X
authors.lastname: Huo
authors.forename: Fu
authors.initials: F
authors.lastname: Yan
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Dingxian
authors.initials: D
authors.lastname: Wang
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Gao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cao
authors.forename: Dewei
authors.initials: D
authors.lastname: Luo
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality; D000072200:Ku Autoantigen; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015996:Survival Rate
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D008156:Luciferases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen