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

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.