Efficacy of Low-Dose Aspirin in Colorectal Cancer Risk Prevention is Dependent on ADH1B and ALDH2 Genotype in Japanese Familial Adenomatous Polyposis Patients
Author:
Mure Kanae1ORCID, Ishikawa Hideki23, Mutoh Michihiro24, Horinaka Mano5, Otani Takahiro6, Suzuki Sadao6ORCID, Wakabayashi Keiji7, Sakai Toshiyuki5, Sato Yasushi, Doyama Hisashi, Tajika Masahiro, Tanaka Shinji, Horimatsu Takahiro, Takeuchi Yoji, Kashida Hiroshi, Tashiro Jun, Ezoe Yasumasa, Nakajima Takeshi, Ikematsu Hiroaki, Hori Shinichiro, Takayama Tetsuji, Ohda Yoshio,
Affiliation:
1. 1Department of Public Health, Wakayama Medical University School of Medicine, Wakayama, Japan. 2. 2Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan. 3. 3Ishikawa Gastroenterology Clinic, Osaka, Japan. 4. 4Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening/Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. 5. 5Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 6. 6Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. 7. 7Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
Abstract
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 (Pinteraction = 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.
Funder
Japan Agency for Medical Research and Development
Publisher
American Association for Cancer Research (AACR)
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