Gastric cancer in relation to the intake of nutrients involved in one-carbon metabolism among MTHFR 677 TT carriers

Background DNA methylation is an important epigenetic process for transcriptional control of human genome including those genes involved in cancer initiation and progression. Clinical studies have suggested that biological explanation to the protective effect of some nutrients could be linked with the DNA methylation. Folate is a primary methyl donor nutrient; it has been shown to play a key role in DNA methylation, repair and synthesis, by acting as co-factors and/or substrates in this metabolic pathway. Likewise, activity of a key enzyme, the methylenetetrahydrofolate reductase (MTHFR) has also been shown to influence DNA methylation. Overall, these findings support the notion that dietary intake as well as genetic factors play a role in one-carbon metabolism. Aim of the study This study is to evaluate the dietary intake of nutrients involved in one-carbon metabolism and the genotype of MTHFR 677 C > T with respect to GC risk. Methods We carried out in January 2004 a population-based case-control study in the metropolitan area of Mexico City. A total of 248 histological confirmed GC patients were recruited from nine tertiary hospitals, along with 478 age and sex-matched controls. Nutrient intake was estimated from food frequency questionnaire; the MTHFR 677C > T genotype was determined by PCR-RFLP analysis. Results A significant reduction in diffuse GC risk was observed for MTHFR 677 TT genotype among individuals with high consumption of folate (OR = 0.23; 95% CI 0.06-0.84), choline (OR = 0.55; 95% CI 0.33-0.9) and Vitamin B₆ (OR = 0.59; 95% CI 0.36-0.96) compared to MTHFR 677 CC + CT carriers. Among subjects with low consumption of methionine, a reduced risk of diffuse GC was also detected (OR = 0.40; 95% CI 0.16-0.97). In contrast, carriers of the MTHFR 677 TT genotype with a low consumption of folate had a significant increased risk of intestinal GC (OR = 1.88 95% CI 1.02-3.47). A folate-MTHFR 677 C > T interaction in the borderline of significance (P = 0.055) was detected. Conclusions It is probable that GC prevention requires dietary recommendations according to the individual genotype; nevertheless, the available information to this respect is still very limited.