title: Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers.
abstract: Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme for the elimination of acetaldehyde, an established animal carcinogen generated by alcohol metabolism. In the presence of ALDH2*2, a mutant allele that is prevalent in East Asians, this enzyme is inactive, leading to excessive accumulation of acetaldehyde. Only among Japanese alcoholic patients has the positive association between this inactive form of ALDH2 and multiple-field cancerization in the upper aerodigestive tract been demonstrated. Whether this finding could be extended to multiple-cancer patients in general is of great interest, because the prevalence of esophageal cancer with other organ cancers has increased dramatically during recent decades in Japan. This study compared the ALDH2 genotypes of groups of male Japanese drinkers who had either esophageal squamous cell carcinomas (SCCs) with (n = 26) or without (n = 48) multiplicity or oropharyngolaryngeal SCCs with (n = 17) or without (n = 29) multiplicity. After adjustments for age and drinking and smoking habits, logistic regression analysis showed significantly increased risk for each multiplicity associated with either esophageal or oropharyngolaryngeal SCCs in the presence of the ALDH2*2 allele (odds ratio, 5.26; 95% confidence interval, 1.08-51.06 and odds ratio, 7.36; 95% confidence interval, 1.29-80.70, respectively). This study is the first to strongly link inactive ALDH2 with the multiple cancer susceptibility of male Japanese drinkers with either esophageal or oropharyngolaryngeal cancers. A simple questionnaire about both current and past facial flushing after drinking a glass of beer was highly sensitive (95.6%) in detecting inactive ALDH2 in these patients and may be useful for identifying high-risk patients.
authors.affiliation: National Institute on Alcoholism, Kurihama National Hospital, Yokosuka, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukuda
authors.forename: Tatsumasa
authors.initials: T
authors.lastname: Haneda
authors.forename: Hoichi
authors.initials: H
authors.lastname: Kato
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Taro
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Igaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tachimori
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000473:pathology; D005483:Flushing / Q000235:genetics; D005838:Genotype; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000209:etiology* / Q000473:pathology; D011795:Surveys and Questionnaires
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial