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Objective  DNA methyltransferase 3b (DNMT3b) plays an important role in abnormal methylation during tumorigenesis. Polymorphism of the  DNMT3b  gene may influence  DNMT3b  activity and be associated with cancer risk. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of the  DNMT3b  gene and susceptibility and prognosis of gastric cancer.    Methods  Four hundred and forty-seven histologically-confirmed gastric cancer cases, 111 gastric atrophy cases and 961 tumor-free controls were enrolled into the study. Five tag SNPs (rs6119954, rs1569686, rs4911107, rs4911259 and rs8118663) of the  DNMT3b  gene were genotyped by TaqMan assay. DNMT3b expression was evaluated in 104 cancer tissues by immunohistochemistry method.    Results  The median follow-up time for 422 gastric patients with prognosis information was 55.1 (51.8–58.5) month. We found that individuals with the rs1569686 variant genotype (TG/GG) were significantly associated with poor prognosis in gastric cancer compared to those carrying the TT genotype (HR = 1.43, 95%CI: 1.02–1.99). This trend was more evident in the long-term survival of gastric cancer. Similar results were observed for the G allele carriers of rs4911107 and T allele carriers of rs4911259 as these two sites were in complete linkage disequilibrium with rs1569686. The rs8118663 GG carriers tended to live shorter than AA/AG genotype (HR = 2.72, 95%CI: 1.45–5.12) in patients living longer than 2.0 years. None of the five SNPs was associated with the risks of gastric cancer or gastric atrophy. And no relationship was found between each of the five SNPs and DNMT3b expression.    Conclusions  This study provides evidence that  DNMT3b  polymorphisms may predict long-term survival of gastric cancer. However, further studies are needed to reveal the underlying biological roles of  DNMT3b  polymorphism.

Polymorphism of DNA Methyltransferase 3b and Association with Development and Prognosis in Gastric Cancer