Aspirin has been shown to protect against
colorectal neoplasms; however, the optimal chemopreventive dose and underlying mechanisms are unclear. We aimed to study the relationship between
prostanoid metabolites and
aspirin's effect on
adenoma occurrence. We used data from the
Aspirin/
Folate Polyp Prevention Study, in which 1,121 participants with a recent
adenoma were randomized to placebo or two doses of
aspirin (81 or 325 mg/d) to be taken until the next surveillance colonoscopy, anticipated about 3 years later. Urinary metabolites of
prostanoids (
PGE-M, PGI-M, and dTxB2) were measured using liquid chromatography/mass spectrometry or GC/NICI-MS in 876 participants near the end of treatment follow-up. Poisson regression with a robust error variance was used to calculate relative risks and 95% confidence intervals.
PGE-M, PGI-M, and dTxB2 levels were 28%, 37%, and 60% proportionately lower, respectively, in individuals who took 325 mg of
aspirin compared with individuals who took placebo (all P < 0.001). Similarly, among individuals who took 81 mg of
aspirin,
PGE-M, PGI-M, and dTxB2 were, respectively, 18%, 30%, and 57% proportionally lower compared with placebo (all P < 0.005). None of the metabolites or their ratios were statistically significantly associated with the risk of
adenoma occurrence. The effect of
aspirin in reducing
adenoma risk was independent of
prostanoid levels.
Aspirin use is associated with lower levels of urinary
prostanoid metabolites. However, our findings do not support the hypothesis that these metabolites are associated with
adenoma occurrence, suggesting that COX-dependent mechanisms may not completely explain the chemopreventive effect of
aspirin on
colorectal neoplasms.