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.
Keywords: single nucleotide polymorphism, rs13181, nasopharyngeal carcinoma, excision repair cross complementation group 2, tumor-free survival, overall survival