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

我们已经报道过大量饮酒与结直肠癌相关，并且醛脱氢酶2基因异型的饮酒者比其他人群的风险更高。推测酒精与结直肠癌的关系可能是通过叶酸缺乏介导的。另一方面，Chen等人（1996）提出了一种假说，认为亚甲基四氢叶酸还原酶（MTHFR）基因的基因型差异也与结直肠癌有关。它在677核苷酸上的C到T的替换引入了与ala(a)和val(V)的遗传多态性。有人提出，V/V纯合子往往缺乏较少的叶酸，因此它们患结直肠癌的风险较低。本研究旨在通过进行病例对照研究来确定他们的假设。病例为在千叶肿瘤中心医院接受手术治疗的179例结肠癌患者和113例直肠癌患者，对照组为161例各种非恶性疾病患者。采用外周血淋巴细胞DNA PCR法检测基因型，并通过自我填写问卷了解其生活方式。在所有男性受试者中，包括病例和对照组，V/V的频率随年龄的变化而降低，从40多岁的19%降至70多岁的10%，饮酒习惯也不一致，饮酒者为17%，不饮酒者为9%。然而，在调整性别、年龄和饮酒习惯后，没有观察到病例和对照组之间的差异。我们没有发现任何证实MTHFR与结直肠癌正相关的证据。

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.