Association between genetic polymorphisms of DNA base excision repair genes and evolution of precancerous gastric lesions in a Chinese population
发表时间：2009-12-16 14:34
Baseexcision repair pathway may play an importantrole inrepairing 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 ribo syltransferase(ADPRT,Val762Ala),8-oxoguanineDNAglycosylase (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/Trp1Trp/Trp genotype had an elevated chance of regression of gastric lesions [adjusted odds ratio (OR) 51.44; 95% confidence interval (CI) 5 1.06–1.96], whereas subjects carrying the XRCC1-399Arg/Gln1Gln/Gln genotype had a decreased chance of regression (OR 5 0.68; 95% CI 5 0.49–0.92).Stratified analysis indicated that an increased risk of progression was observed in subjects carrying the XRCC1-399Arg/Gln1Gln/Gln genotype (OR 5 1.60; 95% CI 5 1.09–2.36) or OGG1-326Ser/Cys1Cys/Cys genotype (OR 5 1.95; 95% CI 5 1.03–3.71) with intestinal metaplasia or dysplasia at baseline or carrying the XRCC1-399Arg/Gln1Gln/Gln genotype and smoking (OR 51.58; 95% CI 5 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 5 1.32–6.08), 2.22 (95% CI 5 1.24–3.98) or 2.27 (95%CI 5 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 ofH.pylori-associated gastric lesions in this high-risk population.
第一署名医院：北京大学肿瘤医院
