アルコール代謝ならびに葉酸代謝酵素の遺伝的多型と大腸がんに関する疫学的研究

点击翻译按钮获取中文摘要

We hae already reported that heavy alcohol drinking is associated with coloectal cancer, and also that the alcohol drinkers with the heteroqygous genotype of aldehyde dehydrogenase 2 gene are in a higher risk than other groups. It was speculated that the alcohol-colorectal cancer relationship might be mediated through folate deprivation. On the other hand, Chen et al. (1996) proposed a hypothesis that a genotype difference in a methylene-tetrahydrofolate reductase (MTHFR) gene is also associated with colorectal cancer. Its C to T substitution at nucleoptide 677 introduced a genetic polymorphism with ala(A) and val(V). It was proposed that the V/V homozygotes tend to be less folate deprived so that they are at a low risk of colorectal cancer.This study aimed to ascertain their hypothesis by conducting a case control study. Cases were 179 colon and 113 rectum cancer patients who were surgically streated in Chiba Cancer Center Hospital, and controls were 161 patients of various non-malignant diseases. The genotypes were tested with PCR method applied on peripheral lymphocyte DNA and informations on their life styles were obtained by a self-administerred questionnaire.In the whole male subjects, including cases and controls, frequency of V/V was reduced age-dependently from 19% in 40's to 10% in 70's, and was also disagreed by alcohol drinking habit with 17% in drinkers and 9% in non-drinkers. However, no difference was observed between the cases and controls after adjusting for genders, ages and the drinking habits. We could not find any confirming evidence for the positive association of MTHFR and colorectal cancer.