[Alcohol and oropharyngolaryngeal and digestive tract cancer].
Epidemiology has demonstrated that alcoholic beverages are causally related to oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer. Among Japanese male alcoholics screened by endoscopy combined with esophageal iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in Asians, exposes them to higher levels of acetaldehyde after drinking and was a strong risk factor for these cancers among Japanese heavy drinkers. Inactive ALDH2 was also associated with synchronous and metachronous multiple esophageal cancers. These results suggest a general role of acetaldehyde, an established animal carcinogen, in carcinogenesis of the human alimentary tract. The oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial production or alcoholic beverages, these organs' inefficient degradation of acetaldehyde enhances the chances for local acetaldehyde-associated carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1, is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative fashion. The responses to a simple questionnaire about both current and past facial flushing after drinking a glass of beer can indicate an individual's ALDH2 phenotype fairly well. Use of this questionnaire to obtain information on ALDH2-associated cancer susceptibility could contribute to the prevention of alcohol-related cancer in Asians.
Yokoyama
A
A
National Institute on Alcoholism, Kurihama National Hospital, Kanagawa 239-0841, Japan.
Omori
T
T
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000434:Alcoholic Beverages / Q000009:adverse effects*; D000437:Alcoholism / Q000150:complications; D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D004067:Digestive System Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D011110:Polymorphism, Genetic
C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde