<title>Abstract</title><sec>
<title>Background</title>
A chemopreventive effect of low-dose aspirin against colorectal tumors was previously found in participants of two Japanese multicenter, double-blind, randomized, placebo-controlled clinical trials investigating the effects of daily aspirin (100 mg/day) for 0.7–2 years on tumor recurrence in colorectal cancer patients whose tumors were excised endoscopically.


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<title>Methods</title>
In the current study, chemopreventive data from single-center subsets having daily aspirin (100 mg/day) were reanalyzed with respect to variations in polymorphic cytochrome P450 2A6 (CYP2A6). From the J-CAPP study, 56 of 311 participants (47 men, 9 women; excluding patients with familial adenomatous polyposis) were genotyped for <italic>CYP2A6*1</italic>, <italic>*4</italic> (whole-gene deletion), <italic>*7</italic> (amino acid substitution), and <italic>*9</italic> (upstream mutation), and from the J-FAPP IV study, 81 of 102 participants (43 men, 38 women; including patients with familial adenomatous polyposis) were also genotyped.


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<title>Results</title>
The chemopreventive effects of daily aspirin were found to be inversely dependent on the predicted enzyme activity of the CYP2A6 phenotype [based on normal genotypes (<italic>CYP2A6*1/*1</italic>,<italic>*7</italic>,<italic>*9</italic>) and impaired genotypes (<italic>CYP2A6*4</italic>,<italic>*7</italic>,<italic>*9/*4</italic>,<italic>*7</italic>,<italic>*9</italic> and <italic>CYP2A6*1/*4</italic>)] among a nonsmoker Japanese cohort without familial adenomatous polyposis.


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<title>Conclusions</title>
The <italic>CYP2A6</italic> wild-type allele could be a candidate biomarker for reduced chemopreventive effects of daily aspirin in a population with wide-ranging CYP2A6 phenotypes with a high frequency of impaired activities resulting from variations and whole-gene deletions. The <italic>CYP2A6</italic> genotypes could be applicable to future personalized treatments for colorectal tumor chemoprevention with daily aspirin.


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