ESOPHAGEAL CANCER AND ALDEHYDE DEHYDROGENASE-2 GENOTYPES IN JAPANESE MALES

Although drinking alcohol is an established esophageal cancer risk fac tor, the mechanisms by which alcohol induces this high-mortality rate cancer are not clear. To help elucidate this problem and develop an im plementable preventive strategy, this genetic epidemiological study fo cused on aldehyde dehydrogenase 2 (ALDH2), the key enzyme for eliminat ion of acetaldehyde generated by alcohol consumption, This enzyme is p olymorphic; its mutant allele, ALDH22, which leads to the enzyme inac tivity, is prevalent in Orientals, This Japanese case-control study of ALDH2-related risk for esophageal squamous cell carcinoma included al coholics (40 cases and 55 controls) and nonalcoholic drinkers (29 case s and 28 controls), The analysis of the results of genotyping these su bjects showed that the increased risk for esophageal cancer in those w ith one ALDH22 allele was substantially higher in both alcoholics (od ds ratio = 7.6; 95% confidence interval = 2.8-20.7) and nonalcoholic d rinkers (odds ratio = 12.1; 95% confidence interval = 3.4-42.8). The r esults strongly suggest that because persons who have this mutant ALDH 22 allele have a high concentration of blood acetaldehyde after drink ing alcohol, acetaldehyde (a recognized animal carcinogen) plays a piv otal role in the pathogenesis of alcohol-related esophageal cancer in humans. These results suggest that to help lower their risk for esopha geal cancer, persons with the ALDH22 allele should be encouraged to r educe their consumption of alcoholic beverages.