Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma
Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma
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DOI：
10.1093/carcin/bgl206
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发表时间：
2007-04-01
期刊：
影响因子：
4.7
通讯作者：
Watanabe, Hiroshi
中科院分区：
文献类型：
--
作者：
Asakage, Takahiro;Yokoyama, Akira;Watanabe, Hiroshi
乙醛脱氢酶-2（ALDH 2）、乙醇脱氢酶-1B（ADH 1B，以前称为ADH 2）和ADH 1C（以前称为ADH 3）的遗传多态性影响酒精的代谢。由ALDH 2 *1/*2编码的无活性ALDH 2和由ADH 1B *1/*1编码的活性较低的ADH 1B增加了东亚饮酒者患食管鳞状细胞癌的风险。这项病例对照研究涉及96名患有口腔和咽鳞状细胞癌的日本男性（43名下咽癌患者和53名口腔/口咽癌患者）和642名无癌症的日本男性。在中度至重度饮酒者（9+单位/周; 1单位= 22 g乙醇）中，ALDH 2 *1/*2分别使总体癌症和下咽癌的风险增加3.61倍和10.08倍，但ALDH 2基因型对口腔/口咽癌的风险没有显著影响。一个简单的酒精冲洗问卷所获得的结果基本上与ALDH 2基因分型所获得的结果。在中度至重度饮酒者中，ADH 1B *1/*1活性较低的男性患下咽癌和口腔/口咽癌的风险显著较高（OR分别为5.56、7.21和4.24）。鉴于ADH 1B和ADH 1C之间的连锁不平衡，ADH 1C基因型对癌症风险没有显著影响。在中度至重度饮酒者中，口腔癌和咽癌的显著独立风险因素是不活跃的ALDH 2 *1/*2，不活跃的ADH 1B *1/*1，经常直接饮用烈性酒精饮料，吸烟和较少摄入绿色-黄色蔬菜。教育这些风险的上呼吸消化道癌症可能是一个有用的新的战略方法，以预防这些癌症在日本。
The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-1B (ADH1B, previously called ADH2), and ADH1C (previously called ADH3) affect the metabolism of alcohol. The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active ADH1B encoded by ADH1B*1/*1 increase the risk of esophageal squamous cell carcinoma in East Asian drinkers. This case-control study involved 96 Japanese men with oral and pharyngeal squamous cell carcinoma (hypopharyngeal cancer in 43 patients and oral/oropharyngeal cancer in 53) and 642 cancer-free Japanese men. The risk of the cancers overall and of hypopharyngeal cancer was increased 3.61- and 10.08-fold, respectively, by ALDH2*1/*2 among moderate-to-heavy drinkers (9+ units/week; one unit = 22 g of ethanol), but the risk of oral/oropharyngeal cancer was not significantly affected by the ALDH2 genotype. The results obtained with a simple alcohol flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping. Among moderate-to-heavy drinkers, men with the less-active ADH1B*1/*1 had a significantly higher risk of the cancers overall, of hypopharyngeal cancer, and of oral/oropharyngeal cancer (OR = 5.56, 7.21 and 4.24, respectively). In view of the linkage disequilibrium between ADH1B and ADH1C, the ADH1C genotype does not significantly affect cancer risk. The significant independent risk factors for oral and pharyngeal cancer overall among moderate-to-heavy drinkers were inactive ALDH2*1/*2, less-active ADH1B*1/*1, frequent drinking of strong alcohol beverages straight, smoking, and lower intake of green-yellow vegetables. Educating these risks for cancer of the upper aerodigestive tract could be a useful new strategic approach to the prevention of these cancers in Japanese.