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

// Jing Wang 1, 2, * , Chengxian Guo 3, * , Xiaochang Gong 1 , Fan Ao 1 , Yuling Huang 1 , Lihua Huang 4 , Yiqiang Tang 1 , Chunling Jiang 1 , Xiaoxue Xie 5 , Qing Dong 1, 6 , Min Huang 1 and Jingao Li 1 1 Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang 330029, China 2 Department of Intensive Care Unit, Jiangxi Cancer Hospital, Nanchang 330029, China 3 Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China 4 Center for Medical Experiments, Third Xiangya Hospital, Central South University, Changsha 410013, China 5 Department of Radiation and Oncology, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, China 6 Department of Graduate Study, Medical School of Nanchang University, Nanchang 330006, China * These authors have contributed equally to this work Correspondence to: Jingao Li, email: lijingao@hotmail.com Keywords: base excision repair (BER) genes, single nucleotide polymorphism (SNP), nasopharyngeal carcinoma (NPC), acute radiation toxicity, short-term efficacy Received: April 07, 2017     Accepted: July 19, 2017     Published: August 10, 2017 ABSTRACT 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.