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 μg/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).

Highlights

  • Gastric cancer is one of the most common malignant diseases worldwide, which is a disease of multiple etiologic factors involving infectious, dietary, environmental and genetic factors (IRAC, 2008)

  • Compared with the Methylenetetrahydrofolate reductase (MTHFR) 677CC genotype, the TT genotype was significantly associated with 2.08 fold risk of gastric cancer when adjusting for potential risk factors

  • The distributions of the MTHFR C677T polymorphisms in the controls were in line with Hardy-Weinberg equilibrium

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Summary

Introduction

Gastric cancer is one of the most common malignant diseases worldwide, which is a disease of multiple etiologic factors involving infectious, dietary, environmental and genetic factors (IRAC, 2008). Individuals who had an intake of folate above 310 μg/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

Results
Conclusion

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