title: Aberrant DNA Methylation of P16, MGMT, and hMLH1 Genes in Combination with MTHFR C677T Genetic Polymorphism in gastric cancer.
abstract: OBJECTIVE
  We aimed to explore the association of P16, MGMT and HMLH1 with gastric cancer and their relation with Methylenetetrahydrofolate reductase (MTHFR).
  
  
  METHODS
  322 gastric patients who were confirmed with pathological diagnosis were included in our study. Aberrant DNA methylation of P16, MGMT and HMLH1 and polymorphisms of MTHFR C677T and A1298C were detected using PCR-RFLP.
  
  
  RESULTS
  The proportions of DNA hypermethylation in P16, MGMT and hMLH1 genes in gastric cancer tissues were 75.2% (242/322), 27.6% (89/322) and 5.3% (17/322), respectively. In the remote normal-appearing tissues, 29.5% (95/322) and 16.1%(52/322) showed hypermethylation in P16 and MGMT genes, respectively. We found a significantly higher proportion of DNA hypermethylation of P16 in patients with N1 TNM stage in cancer tissues and remote normal-appearing tissues (P<0.05). Similarly, we found DNA hypermethylation of MGMT had significantly higher proportion in N1 and M1 TNM stage (P<0.05). Individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues [OR (95% CI)=4.27(1.76-7.84)], and a significant risk was also found in those carrying MTHFR 677CT/TT genotype [OR (95% CI)= 3.27(1.21-4.77)].
  
  
  CONCLUSIONS
  We found the aberrant hypermethylation of cancer-related genes, such as P16, MGMT and HMLH1, could be predictive biomarkers for detection of gastric cancer.
authors.affiliation: Binbin Song, Department of Gastroenterology, Hongqi Hospital, Mudanjiang, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Song
authors.affiliation: Jiang Ai, Department of Gastroenterology, Hongqi Hospital, Mudanjiang, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Ai
authors.affiliation: Xianghong Kong, Department of Gastroenterology, Hongqi Hospital, Mudanjiang, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Kong
authors.affiliation: Dexin Liu, Department of Gastroenterology, Hongqi Hospital, Mudanjiang, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Liu
authors.affiliation: Jun Li, Affiliated Hospital of Sun Yat-sen University of Huzhou, Huizhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
keywords: Aberrant DNA Methylation; Gastric cancer; MGMT; P16; hMLH1