Influence of single nucleotide polymorphisms of DNMT1 gene in survival of patients with gastric cancer after operation

Abstract

Objective To investigate the association between the single nucleotide polymorphisms(SNPs)of DNA methyltransferase 1(DNMT1)gene and the survival of the patients with gastric cancer after operation in the Han population from North China,and to clarify the association between the polymorphisms of DNMT1 gene and prognosis of gastric cancer.Methods A total of 447 gastric cancer patients treated with total gastrectomy were selected into the cohort study.The distribution of genotypic frequencies of five SNPs sites(rs16999593,rs10420321,rs2288349,rs2228611 and rs2228612)of DNMT1 were detected by TaqMan assay.447 cases of gastric cancer patients were followed up.Kaplan-Meier method was used to calculate the survival and draw the survival curves,and Log-rank test was used to compare the differences of overall survival(OS)between the patients with different genotypes.The hazardratio(HR)and 95% confidence interval(CI)were estimated by univariate and multivariate Cox regression analysis.Results Compared with the patients carried GG genotype at the rs2228611 site,the patients with GA/AA genotypes had better prognosis and Longer survival time(52.5months vs 42.9months,Log-rank P=0.006).After adjusting the confounding factors,the patients carried rs2228611GA/AA genotypes had a decreased death risk than the patients with GG genotype(HR 0.68,95% CI:0.50-0.92,P=0.013),suggesting that the polymorphisms of rs2228611 site was an independent influencing factor of prognosis of the patients with gastric cancer after operation.There was no association between the polymorphisms of other sites and the prognosis of gastric cancer.Conclusion The polymorphisms of DNMT1rs2228611GA/AA genotypes can prolong the survival time of the patients with gastric cancer.The polymorphism of DNMT1 could be used as a biomarker to predict the prognosis of gastric cancer.