The Association of Single-Nucleotide Polymorphism rs13181 in ERCC2 with Risk and Prognosis of Nasopharyngeal Carcinoma in an Endemic Chinese Population.

ABSTRACT

OBJECTIVE: We examined whether the single-nucleotide polymorphism (SNP) rs13181 in the gene encoding excision repair cross complementation group 2 (ERCC2) is associated with the risk and prognosis of nasopharyngeal carcinoma (NPC). METHODS: SNPs at rs13181 were genotyped in 439 NPC patients (NPC group) and 431 age- and gender-matched cancer-free controls (control group) from a region of China where NPC is endemic, and frequencies of GG, GT and TT genotypes were compared between the two groups in the case-control study. In a subset of 365 NPC cases, SNPs were examined for potential correlation with tumor-free survival time (TFS) and overall survival (OS). RESULTS: Relative to NPC risk with a TT genotype, NPC risk was similar with GT + GG genotypes (OR 1.052, 95% CI 0.656-1.688), after adjusting for gender, age, smoking history, and immunoglobin A against Epstein-Barr virus capsid antigen (EBV-VCA-IgA) status. Univariate analysis showed that the GG or GT genotype was associated with significantly worse TFS (p<0.001) and OS (p=0.010) than the TT genotype. Prognosis was significantly worse for men than for women (TFS, p=0.045; OS, p=0.031), for T3-T4 classification than for T1-T2 (TFS, p=0.009; OS, p=0.007), for N3 than for N0+N1+N2 (TFS, p<0.001; OS, p<0.001). Based on multivariate analysis, independent risk factors for poor TFS were GG or GT genotype (HR 2.629, 95% CI 1.625-4.254, p<0.001), T3-T4 classification (HR 2.146, 95% CI 1.244-3.701, p=0.006) and N3 (HR 2.527, 95% CI 1.574-4.059, p<0.001). GG or GT genotype (HR 2.217, 95% CI 1.283-3.832, p=0.004), gender (HR 1.989, 95% CI 1.046-3.785, p=0.036), T3-T4 (HR 2.431, 95% CI 1.306-4.526, p=0.005) and N3 (HR 2.693, 95% CI 1.637-4.432, p<0.001) were independent risk factors for poor OS. CONCLUSION: The rs13181 SNP in ERCC2 does not appear to be associated with NPC risk, but it may serve as an independent prognostic factor for NPC recurrence and death.