Genetic polymorphisms of methylenetetrahydrofolate reductase and aldehyde dehydrogenase 2, alcohol use and risk of colorectal adenomas: Self-Defense Forces Health Study.

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.

Maternity testing using mitochondrial DNA analysis.

We examined the maternal relationship in two cases using mitochondrial DNA (mtDNA) analysis. The hypervariable region, HVI in the displacement loop (D-loop) region, was amplified and sequenced. Samples from both cases showed the nucleotide replacements of A to C at positions 16,182 and 16,183, and T to C at position 16,189, giving rise to a C-stretch from position 16,182 to 16,193, in which twelve Cs continued. We were unable to read the region after the C-stretch by forward sequencing in both cases, and it was thought that heteroplasmy was the reason for this. However, there were other identical nucleotide replacements in addition to the C-stretch in both cases. Additionally, nucleotide sequencing was used successfully to demonstrate complete maternal inheritance in all the offspring of eight families over two or three generations. We were therefore able to confirm the maternal relationship in the two present cases, and accordingly we consider that mtDNA sequencing is a very useful method for examining the maternal relationship, especially in cases where the father is not available.