DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms ofDNMT1may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms ofDNMT1gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of theDNMT1gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs ofDNMT1and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91,P=0.007). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91,P=0.010). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of theDNMT1gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients.
In-silico investigations into natural products as nonnucleoside DNA methyltransferase 1 inhibitors for treating epi-mutation in gastric cancer
