ALCOHOL-RELATED CANCERS AND ALDEHYDE DEHYDROGENASE-2 IN JAPANESE ALCOHOLICS

Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde p roduced during alcohol metabolism. In some drinkers, a mutant ALDH2 al lele contributes to diminished activity of the enzyme, dramatically in creasing the risk for esophageal cancer. This study was designed to ev aluate the ALDH2 gene polymorphism as a predictor of the development o f cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyp ing on lymphocyte DNA samples from Japanese alcoholic men (487 cancer- free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophagea l, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multi ple primary cancers in two or three organs). The frequencies of the mu tant ALDH2Y2 allele were significantly higher in alcoholics with orop haryngolaryngeal (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%). Aft er adjustment for age, daily alcohol consumption and amount of cigaret te smoking, significantly increased risks (odds ratios) in the presenc e of the ALDH22 allele were found for oropharyngolaryngeal (11.14), e sophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esoph ageal cancer concomitant with oropharyngolaryngeal and/or stomach canc er (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.