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

Abstract

PurposeTo explore whether polymorphisms in base excision repair (BER) pathway genes are predictors of (chemo)radiotherapy outcome in patients with nasopharyngeal carcinoma (NPC).MethodsWe 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.ResultsWe 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.ConclusionsThe 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.

Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis

“…Most of them evaluated the associations by adopting the strategy of candidate genes. Those candidate genes and pathways include DNA damage and repair involved in doublestrand breaks repair genes [26] and the base excision repair pathway [27]. Other important cellular signaling pathways include the Wnt/β-catenin pathway [28], cell cycle regulated genes, the NF-κB pathways [29], angiogenesis-related genes [30], and GAS5 lncRNAs [31].…”

Potential Functional Variants in DNA Repair Genes Are Associated with Efficacy and Toxicity of Radiotherapy in Patients with Non-Small-Cell Lung Cancer

“…Genetic polymorphisms in XRCC1-194 and XRCC1-399 are also related to the risk of NSCLC [18]. Wang et al [19] have reported that the presence of XRCC1 rs25489 had a significant impact on primary tumor efficacy at the end of radiotherapy and may act as a biomarker for the curative effect of radiotherapy. Zhai et al [20] found that patients with nasopharyngeal carcinoma (NPC) carrying the XRCC1 codon 399 Gln/Gln genotype had a higher rate of tumor regression after radiotherapy.…”

Association between XRCC1 single-nucleotide polymorphisms and susceptibility to nasopharyngeal carcinoma

“…[ 3 ] The difference of clinical response and outcome on NPC suggests the inter-individual variation might play a more important role in NPC susceptibility, [ 4 ] especially the ability of DNA damage repair. [ 5 , 6 ]…”