Efficacy of Low-Dose Aspirin in Colorectal Cancer Risk Prevention is Dependent on ADH1B and ALDH2 Genotype in Japanese Familial Adenomatous Polyposis Patients.

Aspirin has gained great attention as a cancer preventive agent. Our previous study revealed that the low-dose aspirin prevents colorectal tumor recurrence in Japanese patients with colorectal adenomas and/or adenocarcinomas, whereas aspirin increases risks in smokers and has no effects on regular drinkers. Our recent study revealed that aspirin reduces polyp growth in Japanese patients with familial adenomatous polyposis (FAP). In this study, we have studied the association of genotypes of alcohol metabolizing enzymes (ADH1B and ALDH2) on aspirin's efficacy of suppressing polyp growth (≥5 mm) in a total of 81 Japanese patients with FAP. Our study revealed that aspirin showed significant preventive effects for patients with ADH1B -AA and AA+GA types [OR = 0.21; 95% confidence interval (CI), 0.05-0.95, and OR = 0.31; 95% CI, 0.10-0.95, respectively], and for patients with ALDH2 -GG and GG+GA types (OR = 0.10; 95% CI, 0.01-0.92, and OR = 0.29; 95% CI, 0.09-0.94, respectively), but not for patients with ADH1B -GG and GA+GG types, and ALDH2 -AA and GA+AA types. In addition, substantial preventive effects of aspirin were seen for patients with ADH1B -AA type who do not drink regularly (<3 times/week, OR = 0.11; 95% CI, 0.02-0.78), where a statistically significant interaction between aspirin and ADH1B was observed ( P _interaction = 0.036). Results from this exploratory study strongly indicate that aspirin is beneficial in prevention of polyp growth for patients with FAP with ADH1B -AA and AA+GA types, and ALDH2 -GG and GG+GA types. Taken together, we propose ADH1B and ALDH2 as candidate markers for the personalized prevention by aspirin.
Significance: Aspirin is beneficial to patients with FAP with ADH1B -AA and AA+GA types or ALDH2 -GG and GG+GA types. ADH1B and ALDH2 genotypes can be the markers for the personalized prevention of colorectal cancer by aspirin.
Competing Interests: K. Mure, H. Ishikawa, M. Mutoh, K. Wakabayashi, T. Sakai, and S. Tanaka report a grant from Japan Agency for Medical Research and Development during the conduct of the study. Y. Takeuchi reports personal fees from Olympus, Boston Scientific Japan, Daiichi-Sankyo, Miyarisan Pharmaceutical, Asuka Pharmacoceutical, AstraZeneca, EA Pharma, Zeria Pharmaceutical, Fujifilm, Kaneka Medical, and Kyorin Pharmaceutical outside the submitted work. No other disclosures were reported.
(© 2022 The Authors; Published by the American Association for Cancer Research.)