Association of DNA Base-excision Repair XRCC1, OGG1 and APE1 Gene Polymorphisms with Nasopharyngeal Carcinoma Susceptibility in a Chinese Population

Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage includingoxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported toplay a key role in the development of this disease. The base excision repair (BER) pathway can effectively removeoxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1(XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playingimportant roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and exploretheir associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materialsand
Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G)using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models.
Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantlyincreased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18–0.89) in the smokinggroup. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants,was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004).
Conclusion: This is the first studyto focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphismand NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BERgenes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.