Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers
Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers
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DOI：
10.1002/ijc.21583
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发表时间：
2006-04-15
影响因子：
6.4
通讯作者：
Seitz, HK
中科院分区：
文献类型：
--
作者：
Homann, N;Stickel, F;Seitz, HK
长期饮酒与上呼吸消化道癌和肝细胞癌的风险增加有关。通过乙醇脱氢酶（ADH）增加乙醛的产生与发病机制有关。ADH 1C的等位基因ADHIC*1编码具有高生成乙醛能力的酶。到目前为止，ADHD 1C *1等位基因与酗酒者中酒精相关癌症之间的关联仍存在争议。采用聚合酶链反应和限制性片段长度多态性技术检测了818例酒精相关性食管癌（n = 123）、头颈癌（n = 84）和肝细胞癌（n = 86）患者以及酒精性胰腺炎（n = 117）、酒精性肝硬化（n = 217）、合并肝硬化和胰腺炎（n 17）和无胃肠道器官损害的酗酒者（n 174）。ADH 1C *1等位基因和基因型ADH 1C *1/1在酒精相关性癌症患者中的频率显著高于非恶性酒精相关性器官损害患者。使用多变量分析，ADH 1C *1等位基因频率和纯合率与酒精相关癌症的风险增加显著相关（所有情况下p < 0.001）。基因型ADH 1C *1/1与食道癌、肝细胞癌和头颈部癌发生的比值比分别为2.93（CI，1.84-4.67）、3.56（CI，1.33-9.53）和2.2（CI，1.11-4.36）。这些数据表明，基因型ADH 1C *1/1是重度饮酒者发生酒精相关肿瘤的独立危险因素，表明携带这种基因型的个体具有遗传易感性。(c)2005 Wiley-Liss，Inc.
Chronic alcohol consumption is associated with an increased risk for upper aerodigestive tract cancer and hepatocellular carcinoma. Increased acetaldehyde production via alcohol dehydrogenase (ADH) has been implicated in the pathogenesis. The allele ADHIC*1 of ADH1C encodes for an enzyme with a high capacity to generate acetaldehyde. So far, the association between the ADH1C*1 allele and alcohol-related cancers among heavy drinkers is controversial. ADH1C genotypes were determined by polymerase chain reaction and restriction fragment length polymorpism in a total of 818 patients with alcohol-associated esophageal (n = 123), head and neck (n = 84) and hepatocellular cancer (n = 86) as well as in patients with alcoholic pancreatitis (n = 117), alcoholic liver cirrhosis (n = 217), combined liver cirrhosis and pancreatitis (n 17) and in alcoholics without gastrointestinal organ damage (n 174). The ADH1C*1 allele and genotype ADH1C*1/1 were significantly more frequent in patients with alcohol-related cancers than that in individuals with nonmalignant alcohol-related organ damage. Using multivariate analysis, ADH1C*1 allele frequency and rate of homozygosity were significantly associated with an increased risk for alcohol-related cancers (p < 0.001 in all instances). The odds ratio for genotype ADH1C*1/1 regarding the development of esophageal, hepatocellular and head and neck cancer were 2.93 (CI, 1.84-4.67), 3.56 (CI, 1.33-9.53) and 2.2 (Cl, 1.11-4.36), respectively. The data identify genotype ADH1C*1/1 as an independent risk factor for the development of alcohol-associated tumors among heavy drinkers, indicating a genetic predisposition of individuals carrying this genotype. (c) 2005 Wiley-Liss, Inc.