RESUMO
The association between XRCC6/Ku70, an upstream player in the DNA double-strand break repair system, and the risk of nasopharyngeal carcinoma (NPC) was examined. In this case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with NPC risk were evaluated. NPC tissue samples were also assessed for their XRCC6 mRNA and protein expression by real-time quantitative reverse transcription PCR and Western blotting, respectively. With regard to the XRCC6 promoter T-991C, the TC and CC genotypes were associated with a significantly increased risk of NPC compared with wild-type TT genotype (adjusted odds ratio 2.02 and 3.42, 95% confidence interval 1.21-3.32 and 1.28-8.94, P=0.0072 and 0.0165, respectively). The mRNA and protein expression levels for NPC tissues revealed significantly lower XRCC6 mRNA and protein expression in the NPC samples with TC/CC genotypes compared to those with the TT genotype (P=0.0210 and 0.0164, respectively). These findings suggest that XRCC6 may play an important role in the carcinogenesis of NPC and could serve as a chemotherapeutic target for personalized medicine and therapy.
Assuntos
Antígenos Nucleares/genética , Proteínas de Ligação a DNA/genética , Neoplasias Nasofaríngeas/genética , Adolescente , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Carcinoma , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Autoantígeno Ku , Masculino , Carcinoma Nasofaríngeo , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Inquéritos e Questionários , TaiwanRESUMO
BACKGROUND: The Non-homologous end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA double-strand breaks (DSBs), and has been found to be involved in the carcinogenesis of many types of cancers including oral, prostate, breast and bladder cancer. However, the contribution of XRCC6 to childhood leukemia has yet to be studied. In the present study, we investigated the association of XRCC6 genotypes with the risk of childhood leukemia. MATERIALS AND METHODS: Two hundred and sixty-six patients with childhood leukemia and an equal number of age-matched healthy controls recruited in Central Taiwan, were genotyped investigating these polymorphisms' association with childhood leukemia. RESULTS: As for XRCC6 promoter T-991C, patients carrying the TC genotype had a significantly increased risk of childhood leukemia compared with the TT wild-type genotype [odds ratio (OR)=2.30, 95% confidence interval (CI)=1.38-3.84, p=0.0047]. Meanwhile, the genotypes of XRCC6 promoter C-57G, A-31G and intron3 were not statistically associated with childhood leukemia risk. CONCLUSION: Our findings suggest that the XRCC6 genotype could serve as a predictor of childhood leukemia risk and XRCC6 could serve as a target for personalized medicine and therapy.