DNA methyltransferase 3a rs1550117 genetic polymorphism predicts poor survival in gastric cancer patients

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14864-74. eCollection 2015.

Abstract

DNA methyltransferase 3a (DNMT3a) have been suggested to play a crucial role in human cancer prognosis. Single nucleotide polymorphisms (SNPs) in DNMT3a genes may have an impact on the prognosis of cancers. This study aimed to investigate the association between SNPs of DNMT3a gene and prognosis of gastric cancer (GC). Two sites of DNMT3a SNPs, rs1550117 and rs13420827 were selected and genotyped using TaqMan assay in 447 GC patients who received gastrectomy. Effects of genotypes on clinical outcomes of GC were calculated by Kaplan-Meier survival analysis and Cox regression model. We found that the AG or AA genotype of rs1550117 was associated with significantly poorer survival and increased death risk of GC compared with GG genotype (dominant model: HR=1.35, 95% CI=1.01-1.80, P=0.043). Further multivariate Cox regression analysis revealed that in addition to the known factors including male, larger tumor sizes and high clinical stage, rs1550117 variant was an independently predictive factor for survival in GC patients. No significant association was found between rs13420827 genetic variants and GC prognosis. Our findings first demonstrated that DNMT3a rs1550117 polymorphism may be a potential biomarker in predicting overall survival of GC patients.

Keywords: DNA methyltransferase 3a; gastric cancer; overall survival; polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methyltransferase 3A
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality

Substances

  • DNMT3A protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A