Genetic Polymorphisms in ADH1B and ALDH2 Are Associated with Colorectal Tumors in Japan: A Case-Control Study

Abstract

Background: Unlike with esophageal cancer, acetaldehyde levels and genetic polymorphisms in alcohol dehydrogenase have not yet been shown to be contributing factors for colorectal cancer (CRC). This study aimed to clarify the mechanism of CRC development related to alcohol consumption and to the presence of genetic polymorphisms in the alcohol dehydrogenase, ADH1B and aldehyde dehydrogenase, ALDH2. Methods: This was a case-control study (221 cases and 179 controls) in patients with adenomas and intramucosal tumors who underwent endoscopic removal of all tumors. The amount of alcohol consumption was determined using a self-recorded questionnaire, and the tumor information was obtained from colonoscopy results. Blood samples were taken to analyze the following polymorphisms: ALDH2 Glu504Lys and ADH1B His48Arg. Results: The polymorphisms in ADH1B and ALDH2 had little influence on the development of colorectal adenoma or intramucosal cancer. Patients with ALDH2 (Glu/Glu) were more tolerant of alcohol than those with ALDH2 (Glu/Lys and Lys/Lys). Next, we examined certain combinations of the ADH1B genotypes. In the ALDH2 (Glu/Glu) group, an increased risk (OR = 3.4; 95% CI 1.4 - 8.4; P = 0.009) was observed among moderate/heavy drinkers with ADH1B (His/His). In the ALDH2 (Glu/Lys and Lys/Lys) group, an increased risk (OR = 4.2; 95% CI 1.1 - 16.7; P = 0.041) was found among moderate/heavy drinkers with ADH1B (Arg/His and Arg/Arg). Conclusions: ADH1B and ALDH2 activity may be involved in the development of CRC.