Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and alcohol consumption in patients with esophageal cancer.
Alcohol consumption is a risk factor for esophageal cancer. Acetaldehyde, a highly toxic intermediate produced from ethanol, is converted to acetic acid mainly by aldehyde dehydrogenase 2 (ALDH2) in the metabolic pathway of ethanol. Fifty percent of Japanese have inactive ALDH2 due to genetic polymorphism, which is considered to be a risk factor associated with esophageal cancer. In our previous study, we have demonstrated that ALDH2 is expressed in the esophagus with a considerable variation among individuals. In this study, we further investigated the expression of ALDH2 in esophagus and its relationship with risk factors of esophageal cancer. Tissue specimens resected from 51 patients with esophageal cancer were analyzed by immunohistochemistry using ALDH2-antibody. The immuno-staining of ALDH2 in the esophageal epithelium was compared with both the drinking habit and the occurrence of flushing that is closely associated with the ALDH2 deficiency. ALDH2 was not detectable in 8 (16%) among 51 specimens. All of the 8 patients were non- or light-drinkers but not heavy-drinkers. Among 18 patients showing the high level ALDH2 expression in the esophagus, 15 patients (83%) were heavy-drinkers. Although the relationship between the ALDH2 deficiency and drinking habit is not clear, the patients with ALDH2 deficiency tend to be non- or light drinkers while heavy-drinkers tend to have the active form of ALDH2. These results suggest that both inactive and active forms of ALDH2 are induced in the esophagus by heavy drinking and also support a hypothesis that ALDH2 deficiency might be a high-risk factor of esophageal cancer for the individuals having a heavy-drinking habit. To our knowledge, this is the first study demonstrating the induction of ALDH2 in the esophagus by ethanol consumption.
Morita
Masaru
M
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Kitakyushu 807-8555, Japan.
Oyama
Tsunehiro
T
Kagawa
Norio
N
Nakata
Shoji
S
Ono
Kenji
K
Sugaya
Masakazu
M
Uramoto
Hidetaka
H
Yoshimatsu
Takashi
T
Hanagiri
Takeshi
T
Sugio
Kenji
K
Kakeji
Yoshihiro
Y
Yasumoto
Kosei
K
D000428:Alcohol Drinking; D000437:Alcoholism / Q000209:etiology; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000201:enzymology*; D004938:Esophageal Neoplasms / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D005483:Flushing / Q000209:etiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans
D000444:Aldehyde Dehydrogenase