Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics.
Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde produced during alcohol metabolism. In some drinkers, a mutant ALDH2 allele contributes to diminished activity of the enzyme, dramatically increasing the risk for esophageal cancer. This study was designed to evaluate the ALDH2 gene polymorphism as a predictor of the development of cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyping on lymphocyte DNA samples from Japanese alcoholic men (487 cancer-free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophageal, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multiple primary cancers in two or three organs). The frequencies of the mutant ALDH2*2 allele were significantly higher in alcoholics with oropharyngolaryngeal (52.9%), esophageal (52.9%), stomach (22.4%), colon (21.7%) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (78.6%), than in cancer-free alcoholics (9.0%). After adjustment for age, daily alcohol consumption and amount of cigarette smoking, significantly increased risks (odds ratios) in the presence of the ALDH2 *2 allele were found for oropharyngolaryngeal (11.14), esophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.20) but not for liver or other cancers. These results suggest a general role of acetaldehyde, a recognized animal carcinogen, in the development of human cancers.
Yokoyama
A
A
National Institute on Alcoholism, Kurihama National Hospital, Yokosuka, Kanagawa, Japan.
Muramatsu
T
T
Ohmori
T
T
Yokoyama
T
T
Okuyama
K
K
Takahashi
H
H
Hasegawa
Y
Y
Higuchi
S
S
Maruyama
K
K
Shirakura
K
K
Ishii
H
H
D000328:Adult; D000437:Alcoholism / Q000201:enzymology*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics
C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial