Aberrant DNA methylation of P16, MGMT, hMLH1 and hMSH2 genes in combination with the MTHFR C677T genetic polymorphism in gastric cancer

Asian Pac J Cancer Prev. 2013;14(5):3139-42. doi: 10.7314/apjcp.2013.14.5.3139.

Abstract

Associations of P16, MGMT, hMLH1 and hMLH2 with gastric cancer and their relation with MTHFR status in gastric patients who were confirmed with pathological diagnosis were assessed. Aberrant DNA methylation of P16, MGMT, hMLH1 and hMLH2 and polymorphisms of MTHFR C677T were assayed. The proportional DNA hypermethylation in P16, MGMT, hMLH1 and hMLH2 in cancer tissues was significantly higher than in remote normal-appearing tissues. DNA hypermethylation of P16 and MGMT was correlated with the T and N stages. Individuals with homozygotes (TT) of MTHFR C677T had significant risk of hypermethylation of MGMT in cancer tissues [OR (95% CI)= 3.47(1.41-7.93)]. However, we did not find association between polymorphism in MTHFR C677T and risk of hypermethylation in P16, MGMT, hMLH1 and hMLH2 genes either in cancer or remote normal-appearing tissues. Aberrant hypermethylation of P16, MGMT, hMLH1 and hMLH2 could be predictive of gastric cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Genes, p16*
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics*
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Tumor Suppressor Proteins / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MLH1 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • DNA Modification Methylases
  • MGMT protein, human
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes