Hori H, Kawano T, Endo M, Yuasa Y
First Department of Surgery, Tokyo Medical and Dental University School of Medicine, Japan.
J Clin Gastroenterol. 1997 Dec;25(4):568-75. doi: 10.1097/00004836-199712000-00003.
Many human cancers are caused by synthetic or natural chemical compounds in the environment. Esophageal squamous cell carcinoma has been reported to be epidemiologically associated with tobacco and alcohol consumption. We studied the association between genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and esophageal squamous cell carcinoma susceptibility. We examined genetic polymorphisms of the CYPIA1, GSTM1, CYPIIE1, ADH2, and ALDH2 genes in 94 Japanese patients with esophageal squamous cell carcinoma and 70 unrelated healthy Japanese persons. There were no significant differences between healthy controls and patients with esophageal cancer in the polymorphisms of the CYPIA1, GSTM1, and CYPIIE1 genes. On the other hand, there were significant differences in the ADH2 and ALDH2 polymorphisms between healthy controls and esophageal cancer patients. The ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) genotypes were independently and significantly higher in esophageal cancer patients than in healthy controls. Furthermore, persons with the combined genotypes ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) were at extraordinarily high risk for esophageal squamous cell carcinoma, with an odds ratio of 17.9 (p < 0.001). Thus polymorphisms of alcohol-metabolizing enzymes, that is, ADH2 and ALDH2, may be useful for screening patients at high risk for esophageal cancer, which might facilitate clarification of esophageal tumorigenesis and prevention of esophageal cancer.
许多人类癌症是由环境中的合成或天然化学化合物引起的。据报道，食管鳞状细胞癌在流行病学上与烟草和酒精消费有关。我们研究了烟草和酒精相关代谢酶的基因多态性与食管鳞状细胞癌易感性之间的关联。我们检测了94例日本食管鳞状细胞癌患者和70名无血缘关系的健康日本人中CYPIA1、GSTM1、CYPIIE1、ADH2和ALDH2基因的多态性。CYPIA1、GSTM1和CYPIIE1基因的多态性在健康对照组和食管癌患者之间没有显著差异。另一方面，健康对照组和食管癌患者在ADH2和ALDH2多态性方面存在显著差异。食管癌患者中ADH2(1)/ADH2(1)和ALDH2(1)/ALDH2(2)基因型独立且显著高于健康对照组。此外，ADH2(1)/ADH2(1)和ALDH2(1)/ALDH2(2)联合基因型的个体患食管鳞状细胞癌的风险极高，优势比为17.9（p<0.001）。因此，酒精代谢酶即ADH2和ALDH2的多态性可能有助于筛查食管癌高危患者，这可能有助于阐明食管肿瘤发生机制并预防食管癌。
