Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population

Stefania Boccia, Francesco Gianfagna, Roberto Persiani, Antonio La Greca, Dario Arzani, Stefano Rausei, Domenico D'Ugo, Paolo Magistrelli, Paolo Villari, Cornelia M. Van Duijn, Gualtiero Ricciardi

Research output: Contribution to journalArticlepeer-review

Abstract

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the metabolism of folate, which provides a methyl donor for DNA methylation and deoxynucleoside synthesis. We performed a case-control study to explore the relationship between two common MTHFR polymorphisms (C677T and A1298C), their combination and interaction with environmental exposures, on gastric adenocarcinoma susceptibility and progression in an Italian population. One hundred and two cases and 254 hospital controls, matched by age and gender, were enrolled. Individuals carrying the MTHFR 677T allele showed an increased risk of gastric cancer (odds ratio (OR) 1.62, 95% confidence interval (CI) 0.98-2.67), particularly among ever smokers (OR 2.10, 95% CI 1.07-5.33) and, among 677 TT individuals, those with a low intake of fruit and vegetables (OR 2.18, 95% CI 1.05-4.54). The strongest effect, however, was noted for the MTHFR 677 TT genotype among the diffuse gastric cancer histotype (OR 2.92, 95% CI 1.12-7.60). No association was detected for the effect of MTHFR A1298C polymorphism. Survival analysis did not show any association between each polymorphism on the overall survival, although when the analysis was restricted to the first year of follow-up after the surgical intervention an improved survival was noted among MTHFR 677 CC subjects compared with the T allele carriers (p value for log-rank test 0.02). In conclusion, MTHFR 677 (any T genotype) appears to modulate an individual's susceptibility to gastric cancer, particularly when combined with cigarette smoking and among those with a low intake of fruit and vegetables. Our results also suggest that an aberrant DNA methylation pattern, through impaired folate metabolism, might play a key role in gastric carcinogenesis. A possible survival effect of the MTHFR C677T genotype in gastric cancer patients deserves further investigations with larger sample sizes.

Original languageEnglish
Pages (from-to)635-644
Number of pages10
JournalBiomarkers
Volume12
Issue number6
DOIs
Publication statusPublished - Nov 2007

Keywords

  • Diffuse gastric cancer
  • Effect modification smoking
  • Gastric cancer
  • Genetic susceptibility
  • Methylenetetrahydrofolate reductase (MTHFR)
  • Survival

ASJC Scopus subject areas

  • Biotechnology
  • Toxicology

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