Genetic polymorphisms of methylenetetrahydrofolate reductase and aldehyde dehydrogenase 2, alcohol use and risk of colorectal adenomas: Self-Defense Forces Health Study
Genetic polymorphisms of methylenetetrahydrofolate reductase and aldehyde dehydrogenase 2, alcohol use and risk of colorectal adenomas: Self-Defense Forces Health Study
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DOI：
10.1111/j.1349-7006.2005.00077.x
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发表时间：
2005-08-01
期刊：
影响因子：
5.7
通讯作者：
Ikeda, N
中科院分区：
文献类型：
--
作者：
Hirose, M;Kono, S;Ikeda, N
亚甲基四氢叶酸还原酶是叶酸代谢中的关键酶，影响 DNA 合成和甲基化，并可能与结直肠癌发生有关。酒精和乙醛对叶酸代谢有不利影响。本研究通过一项病例对照研究，对在两家自卫队医院接受退休前健康检查的自卫队男性官员进行病例对照研究，探讨了功能性 MTHFR C677T 和 ALDH2 多态性与结直肠腺瘤与饮酒的关系。研究对象为 452 例结直肠腺瘤病例和 1050 例接受全结肠镜检查的无息肉对照者。使用从血沉棕黄层提取的基因组DNA通过PCR-RFLP方法确定基因型。对年龄、医院、SDF排名、体重指数、吸烟年数和饮酒量进行了统计调整。 MTHFR C677T 和 ALDH2 均未显示与结直肠腺瘤存在可测量的关联。虽然大量饮酒与结直肠腺瘤风险适度增加相关，但这两种多态性均未显示出对酒精与结直肠腺瘤之间关联的显着影响。与携带 ALDH2*1/1 和 MTHFR 的个体相比，携带变异等位基因 ALDH2*2 和 MTHFR 677T 的个体患结直肠腺瘤的风险降低，所有腺瘤的调整后比值比为 0.70（95% 置信区间 0.49-1.00），大腺瘤（>= 5 mm）的调整后比值比为 0.57（0.34-0.95）。 677CC 基因型组合。这些发现可能被解释为表明叶酸抑制结直肠腺瘤的生长，但还需要进一步证实。
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 allelesALDH2*2 and MTHFR 677Thad 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 (>= 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.