Breast cancer risk, dietary intake, and methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms

Diet plays an important role in DNA methylation, synthesis, and repair; intake has been associated with breast cancer. The folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR) is polymorphic at nucleotides 677 (C → T), resulting in allozymes with altered activity and is thus believed to cause interindividual differences in cancer risk susceptibility. I evaluated this polymorphism and its effect on the food intake and breast cancer risk association in a population-based case-control study of 100 breast cancer cases and 100 controls using a real-time PCR based assay. All subjects completed in-person interviews, which included a food-frequency questionnaire. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals, after adjusting for potential confounding factors. Cases and controls were similar in the distribution of MTHFR polymorphisms at codon 677 (41.4% cases and 41.8% controls carried the T allele). An inverse association of breast cancer risk with food intake was observed in all genotype groups, particularly among subjects with the 677TT genotype. Compared with those with the 677CC genotype and high food intake frequency, the adjusted odds ratios (95% confidence intervals) associated with low food intake were 1.94 (1.15–3.26), 2.17 (1.34–3.51), and 2.51 (1.37–4.60) for subjects who had CC, CT, and TT genotypes (P for interaction, 0.05). Results of this study suggest that the MTHFR C677T polymorphism may modify the association between dietary intake and breast cancer risk.