Methylenetetrahydrofolate reductase, diet, and risk of colon cancer

Individuals with different forms of the 5,10-methylenetetrahydrofolate redu ctase (MTHFR) gene, carriers of the C677T mutation versus wild type, show d ifferences in enzyme levels; these differences have been hypothesized to he related to DNA methylation and, perhaps, to the nucleotide pool size. Usin g data from an incident case-control study, we evaluated the combined effec t of dietary intake of folate, methionine, vitamin B-6, vitamin B-12, and a lcohol and various forms of the MTHFR gene on risk of colon cancer. Individ uals homozygous for the variant form of the MTHFR gene (TT) had a slightly lower risk of colon cancer than did individuals who were wild type [CC, odd s ratio (OR) = 0.8, 95% confidence interval (CI) = 0.6-1.1 for men; and OR = 0.9, 95% CI = 0.6-1.2 for women]. High levels of intake of folate, vitami n B-6, and vitamin B-12 were associated with a 30-40% reduction in risk of colon cancer among those with the TT relative to those with low levels of i ntake who were CC genotype, Associations were stronger for proximal tumors, in which high levels of intake of these nutrients were associated with a h alving of risk among those with the TT genotype, The inverse association wi th high levels of these nutrients in those with the TT genotype was stronge r among those diagnosed at an older age. Although imprecise, the inverse as sociation with the low-risk diet that was high in folate and methionine and without alcohol was observed for both the TT genotype (OR = 0.4 95% CI = 0 .1-0.9) and the CC/CT genotype (OR = 0.6, 95% CI = 0.4-1.0), but this assoc iation was not seen with the high-risk diet for either the TT or CC/CT geno type, Although associations were generally weak, these findings suggest tha t those with differing MTHFR genotypes may have different susceptibilities to colon cancer, based on dietary consumption of folate, vitamin B-6, and v itamin B-12.