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Diet Folate, DNA Methylation and Polymorphisms in Methylenetetrahydrofolate Reductase in Association with the Susceptibility to Gastric Cancer

  • Gao, Shang (Department of Anthropotomy, School of Basic Medicine, Inner Mongolia Medical University) ;
  • Ding, Li-Hong (Department of Internal Medicine, Affiliated Hospital, Inner Mongolia Medical University) ;
  • Wang, Jian-Wei (Department of Anthropotomy, School of Basic Medicine, Inner Mongolia Medical University) ;
  • Li, Cun-Bao (Department of Biochemical and Molecular Biology, Affiliated Hospital, Inner Mongolia Medical University) ;
  • Wang, Zhao-Yang (Department of General Surgery, Affiliated Hospital, Inner Mongolia Medical University)
  • Published : 2013.01.31

Abstract

Methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with DNA methylation, an epigenetic feature frequently found in gastric cancer. We conducted a case-control study to explore the association of MTHFR C677T polymorphisms with gastric cancer risk and its relation with the DNA methylation of COX-2, MGMT, and hMLH1 genes. Genotyping of P16, MGMT and HMLH1 was determined by methylation-specific PCR after sodium bisulfate modification of DNA, and genotyping of MTHFR C677T was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. Folate intake was calculated with the aid of a questionnaire. Compared with the MTHFR 677CC genotype, the TT genotype was significantly associated with 2.08 fold risk of gastric cancer when adjusting for potential risk factors. Individuals who had an intake of folate above $310{\mu}g$/day showed protective effects against gastric cancer risk. The effect of MTHFR C677T polymorphisms on the risk of gastric cancer was modified by folate intake and methylation status of MGMT (P for interaction <0.05).

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