Abstract B99: Determinants of aspirin metabolism in healthy individuals

Regular use of aspirin is associated with lower colon cancer risk. High inter-individual variation in aspirin metabolism has been attributed to several factors, including sex, concomitant use of other drugs or alcohol, urine pH, ethnicity, and variants in metabolizing enzymes involved in glucuronidation of aspirin metabolites [i.e., UDP glucuronosyltransferases (UGT)]. However, little is known about the impact of other exposures, including dietary factors. Dietary constituents of citrus fruits, cruciferous vegetables and soy have been shown to induce UGT. Higher intakes may alter UGT activity and affect the ratio of aspirin metabolites excreted. We evaluated, cross-sectionally, whether urinary excretion of aspirin [ASA] and its metabolites (salicylic acid [SA], salicyluric acid [SUA], salicyluric phonolic glucuronide [SUPG], salicyl acyl and phenolic acid glucuronides [SAG/SPG]) differed by UGT1A6 genotype and dietary factors. Following an oral dose of 650 mg aspirin, healthy men (N=264) and women (N=264), 20–40 years, collected urine over an 8-h period. Participant exclusion criteria included medical history of gastrointestinal, hepatic or renal disorders, and exposure to non-dietary factors known to influence biotransformation enzymes, e.g., medications, excessive alcohol, and smoking. FFQ data were available for 481 participants. Multiple linear regression was used to determine whether there were differences in aspirin metabolism by UGT1A6 genotype, or daily intake of protein, total fruit or vegetable intake, and soy, citrus and cruciferous vegetable intake, adjusted for body mass index (BMI), age, sex, ethnicity, urine volume and pH, and energy intake. There were statistically significant differences in the ratios of metabolites excreted, (specific metabolite/sum of metabolites), between sexes and between ethnic groups. Men excreted more SUA (P Of the factors evaluated, ethnicity and sex were the greatest, albeit modest, contributors to variability in aspirin metabolism (R2=2−13%), whereas UGT1A6 had no effect. Our results also suggest that diet may influence aspirin metabolism, but the effects do not appear to be via glucuronidation. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B99.