Association between genetic polymorphisms of DNA base excision repair genes and evolution of precancerous gastric lesions in a Chinese population

Abstract

Base excision repair pathway may play an important role in repairing DNA damage related to Helicobacter pylori-induced inflammatory process. To evaluate the association between genetic polymorphisms of X-ray repair cross-complementing group 1 (XRCC1, Arg194Trp and Arg399Gln), adenosine diphosphate ribosyl transferase (ADPRT, Val762Ala), 8-oxoguanine DNA glycosylase (OGG1, Ser326Cys) and apurinic/apyrimidinic endonuclease 1 (APE1, Asp148Glu) and evolution of H.pylori-associated precancerous gastric lesions, a population-based cohort study was conducted in Linqu County, a high-risk area of gastric cancer in China. Genotypes were determined by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography and PCR-restriction fragment length polymorphism analysis in 1281 H.pylori-infected subjects. We found that subjects carrying the combined XRCC1-194Arg/Trp+Trp/Trp genotype had an elevated chance of regression of gastric lesions [adjusted odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.06-1.96], whereas subjects carrying the XRCC1-399Arg/Gln+Gln/Gln genotype had a decreased chance of regression (OR = 0.68; 95% CI = 0.49-0.92). Stratified analysis indicated that an increased risk of progression was observed in subjects carrying the XRCC1-399Arg/Gln+Gln/ Gln genotype (OR = 1.60; 95% CI = 1.09=2.36) or OGG1-326Ser/Cys+Cys/Cys genotype (OR = 1.95; 95% CI = 1.03-3.71) with intestinal metaplasia or dysplasia at baseline or carrying the XRCC1-399Arg/Gln+Gln/Gln genotype and smoking (OR = 1.58; 95% CI = 1.02-2.45). Furthermore, a significantly increased risk of progression was observed in subjects carrying one or two hazard genotypes of XRCC1-399 or OGG1-326, the OR was 2.83 (95% CI = 1.32-6.08), 2.22 (95% CI = 1.24-3.98) or 2.27 (95% CI = 1.26-4.10), respectively. These findings suggest that genetic polymorphisms in XRCC1-Arg194Trp, XRCC1-Arg399Gln and OGG1-Ser326Cys may play important roles in the evolution of H.pylori-associated gastric lesions in this high-risk population. © The Author 2009. Published by Oxford University Press. All rights reserved.