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

UNLABELLED

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 -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 -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 -GG and GA+GG types, and -AA and GA+AA types. In addition, substantial preventive effects of aspirin were seen for patients with -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 was observed ( = 0.036). Results from this exploratory study strongly indicate that aspirin is beneficial in prevention of polyp growth for patients with FAP with -AA and AA+GA types, and -GG and GG+GA types. Taken together, we propose and as candidate markers for the personalized prevention by aspirin.

SIGNIFICANCE

Aspirin is beneficial to patients with FAP with -AA and AA+GA types or -GG and GG+GA types. and genotypes can be the markers for the personalized prevention of colorectal cancer by aspirin.