A case-control study on alcohol drinding habit, ALDH2 genotype and colorectal cancer.

通过病例对照研究，探讨饮酒习惯在结直肠癌发病中的可能作用。~1997年间在千叶肿瘤中心医院手术治疗的结肠癌243例，直肠癌147例。对照组为1124人，包括良性疾病患者和健康检查项目的工作人员。他们的生活方式，如饮酒、吸烟和饮食习惯的信息是通过自填式问卷收集的。对部分受试者(210例和303例对照)，用聚合酶链式反应(PCR)方法进行ALDH2基因分型，检测酒精耐受性。由于乙醛脱氢酶基因的多态性，乙醛脱氢酶活性在日本人群中表现出个体间的差异，包括耐酒精的1/1纯合子、中间的1/2杂合子和不耐受的2/2杂合子。根据单因素分析和卡方检验，日常饮酒量、频繁的肉类摄入量以及不规律、匆忙和过度的饮食习惯等因素都与结肠癌和直肠癌显著相关，而很少摄入牛奶和鱼只与直肠癌相关。每日吸烟量、水果和蔬菜的摄入量在病例组和对照组之间无差异。即使在进行多变量Logistic回归分析后，这些结果也保持不变。如果将ALDH2基因型纳入多因素分析，则该基因型而不是饮酒与结肠癌显著相关，表明杂合子中酶活性降低是结肠癌的危险因素。这在乙状结肠癌中最为突出。没有发现直肠癌有这种关系。结论：过量饮酒是结直肠癌的危险因素，ALDH2杂合子是结肠癌的高危人群。

A case-control study was conducted to explore a possible etiological role of alcohol drinking habit in colorectal cancer. Cases were 243 colon and 147 rectum cancer patients who were surgically treated in Chiba Cancer Center Hospital during the period 1989 through 1997. Controls were 1,124 persons including both patients of benign diseases and attendants of a health check program. Information on their life styles such as drinking, smoking and dietary habits was collected by a self-administered questionnaire. For a part of them (210 cases and 303 controls), alcohl tolerance was also checked by a DNA test of ALDH2 genotypes with the PCR method. Japanese population shows inter-individual variation of aldehyde dehydrogenase activity due to a polymorphism of this gene, with alcohol tolerant 1/1 homozygotes, intermediate 1/2 heterozygotes and intolerant 2/2 homozygotes.According to a uni-variate analysis with the chi-square statistical test, the factors such as daily amount of alcohol consumption, frequent intake of meat, and irregular, hastened and excess meal habits were all significantly associated with both colon and rectum cancers, whereas infrequent intake of milk and fish was associated only with rectum cancer. Daily amount of tobacco smoked, intake frequency of fruits and vegetables were not different between cases and controls. These results remained unchanged even after a multi-variate logistic regression analysis was performed. If the ALDH2 genotype was included in the multi-variate analysis, this genotype instead of alcohol consumption showed signficant association with colon cancer, indicating that reduced enzyme activity in the heterozygotes is a risk factor for colon cancer. This is most prominent for sigmoid colon cancer. No such relation was found for rectum cancer. It is concluded that excess alcohl drinking is a risk factor for colorectal cancer and that the heterozygotes of ALDH2 are especially a high-risk group for colon cancer.