The methylenetetrahydrofolate reductase 677C -> T polymorphism and distal colorectal adenoma risk

A common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) ge ne, where a cytosine at nucleotide 677 is replaced by a thymine (677C-->T), is associated with enzyme thermolability and a reduction in the conversion of 5,10-methyltetrahydrofolate (5,10-MTHF) into 5-methyltetrahydrofolate. We assessed the association between homozygosity for the MTHFR 677CT genoty pe (TT) and colorectal adenoma risk in a large sigmoidoscopy-based case-con trol study of members of a prepaid health plan in Los Angeles, MTHFR genoty pe was determined for 471 cases and 510 age-, sex-, clinic-, and sigmoidosc opy-date-matched controls. Information on RBC and plasma folate levels were analyzed for 331 cases and 350 controls. When compared with the presence o f at least one wild-type allele (CT/CC), the odds ratio (OR) for the TT gen otype was 1.19 [95% confidence interval (CI), 0.77-1.76] after adjusting fo r race and the matching factors. Compared with those in the lowest quartile s of RBC and plasma folate and a wild-type allele, adenoma risk was increas ed for TT homozygotes in the lowest folate quartiles (genotype: OR, 2.04 an d 95% CI, 0.6-7.0; OR, 1.84 and 95% CI, 0.6-7.0 for RBCs and plasma folate, respectively) and decreased in TT homozygotes in the highest quartiles (ge notype: OR, 0.82 and 95% CI, 0.32-2.10; OR, 0.65 and 95% CI, 0.22-1.95, res pectively), There was also a significant interaction between TT genotype an d the increased adenoma risk associated with alcohol. These data are consis tent with an interaction between MTHFR genotype and folate availability.