Alcohol dehydrogenase and aldehyde dehydrogenase polymorphisms and colorectal cancer: The Fukuoka Colorectal Cancer Study

Alcohol dehydrogenase and aldehyde dehydrogenase are key enzymes in alcohol metabolism and therefore may be of importance to colorectal cancer development. The present case-control study was conducted to determine the influence of ADH2, ADH3 and ALDH2 polymorphisms in Fukuoka, Japan, with 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly from the study area. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for sex, age class, area, and alcohol use. Individuals with the allele 47Arg of the ADH2 polymorphism (slow metabolizers) had a statistically significant increase in risk, with an adjusted OR of 1.32 (95% CI = 1.07-1.63), compared with those having the ADH2* 47His/His genotype. This association was not affected by the level of alcohol consumption. The ADH3 polymorphism showed no measurable association with the risk of colorectal cancer on either overall analysis or stratified analysis with alcohol use. The heterozygous ALDH2* 487Glu/Lys genotype was not associated with an increase in the risk of colorectal cancer (adjusted OR 0.89, 95% CI = 0.71-1.13) compared with the ALDH2 * 487Glu/Glu genotype. Rather unexpectedly, the homozygous ALDH2* 487Lys/Lys genotype was related to a statistically significantly decreased risk of colorectal cancer (adjusted OR 0.55, 95% CI = 0.33-0.93). It is unlikely that acetaldehyde metabolism determined by ALDH2 polymorphism contributes to the risk of colorectal cancer, whereas the role of ADH2 polymorphism deserves further investigation.