A METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM AND THE RISK OF COLORECTAL-CANCER

We examined the relationship of a common polymorphism (C-667-->T) of t he methylenetetrahydrofolate reductase (MTHFR) gene with the risk of c olorectal cancer in a case-control study conducted in the Health Profe ssionals Follow-up Study. MTHFR genotypes were ascertained from blood samples among 144 men previously diagnosed with colorectal cancer and 627 controls. The adjusted odds ratio (OR) for the MTHFR valiant homoz ygous (val/val), genotype was 0.57 [95% confidence interval (CI), 0.30 -1.06], sigh dietary intake of methionine (OR, 0.27; 95% CI, 0.06-1.20 ) and low consumption of alcohol (OR, 0.11; 95% CI, 0.01-0.85) were as sociated with reduced incidence of colorectal cancer, Alcohol intake t vas a stronger risk factor among men with the val/val genotype (P, tre nd = 0.01), and consumption of five or more alcoholic drinks per week abolished the reduced risk of colorectal cancer among val/val individu als (P, interaction = 0.02). The inverse association of methionine wit h colorectal cancer risk was slightly stronger among individuals with the MTHFR val/val genotype. These data suggest that dietary methyl sup ply is particularly critical among MTHFR val/val individuals, When die tary methyl supply is high, MTHFR val/val individuals may be at reduce d risk of colorectal cancer probably because higher levels of 5,10-met hylenetetrahydrofolate may prevent imbalances of nucleotide pools duri ng DNA synthesis. In contrast, when 5-methyltetrahydrofolate is deplet ed by alcohol consumption, val/val individuals may be less able to com pensate, leading to potentially oncogenic alterations in DNA methylati on.