The impacts of genetic polymorphisms in genes of base excision repair pathway on the efficacy and acute toxicities of (chemo) radiotherapy in patients with nasopharyngeal carcinoma

Purpose: To explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo) radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC). Methods: We genotyped five potentially functional single nucleotide polymorphisms (SNPs) of three genes in the BER pathway in 174 NPC patients who were treated with (chemo) radiotherapy. Sequenom MassArray was used for SNPs analysis. The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Acute radiation toxicity was scored using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) acute radiation morbidity scoring criteria. Logistic regression was employed to assess the multivariate analyses. Results: We found that the wide genotype GG of X-ray repair cross-complementing 1 (XRCC1) rs25489 (GG vs GA: OR=3.833, 95% CI=1.512-9.714, P=0.005; GG vs GA+AA: OR=3.610, 95% CI=1.496-8.713, P=0.004) and the wide genotype CC of 8-oxoguanine DNA glycosylase (OGG1) rs1052133 (CC vs GG: OR=0.263, 95% CI=0.073-0.951, P=0.042; CC vs CG+GG: OR=0.454, 95% CI=0.195-1.053, P=0.066) were positively and negatively associated with primary tumor efficacy at the end of radiotherapy, respectively. By contrast, no association was found between BER gene polymorphisms and the treatment outcomes at 3 months post-treatment or the treatment-related acute toxicities. Conclusions: The SNPs of the BER genes may act as biomarkers for the curative effect of (chemo) radiotherapy. Further study with long-time follow-up and large population is needed for accurate assessment.