Methylenetetrahydrofolate reductase is a key
enzyme in
folate metabolism, which affects
DNA synthesis and methylation and is possibly linked to colorectal
carcinogenesis. Alcohol and
acetaldehyde have an adverse effect on
folate metabolism. This study investigated the relationship of functional MTHFR C677T and ALDH2 polymorphisms to colorectal
adenomas with reference to alcohol consumption in a case-control study of male officials in the Self-Defense Forces (SDF) who received a preretirement health examination at two SDF hospitals. The study subjects were 452 cases of colorectal
adenoma and 1050 controls with no
polyp who underwent total colonoscopy. Genotypes were determined by the PCR-RFLP method using genomic
DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index, cigarette-years and alcohol intake. Neither MTHFR C677T nor ALDH2 showed a measurable association with colorectal
adenoma. While high alcohol consumption was associated with a moderately increased risk of colorectal
adenoma, neither of the two polymorphisms showed a significant effect on the association between alcohol and colorectal
adenoma. Individuals with the variant alleles ALDH2*2 and MTHFR 677T had a decreased risk of colorectal
adenomas, showing adjusted odds ratios of 0.70 (95% confidence interval 0.49-1.00) for all
adenomas and 0.57 (0.34-0.95) for large
adenomas (> or = 5 mm), as compared to individuals with ALDH2*1/1 and MTHFR 677CC genotypes combined. The findings may be interpreted as suggesting that
folate inhibits the growth of colorectal
adenomas, but further confirmation is needed.