Urinary Metabolites of Prostanoids and Risk of Recurrent Colorectal Adenomas in the Aspirin/Folate Polyp Prevention Study (AFPPS)

• Authors: Veronika Fedirko, Emory University; Patrick T. Bradshaw, University of North Carolina; Jane C. Figueiredo, University of Southern California, Los Angeles; Robert S. Sandler, University of North Carolina; Elizabeth L. Barry, Geisel School of Medicine at Dartmouth; Dennis J. Ahnen, Department of Veterans Affairs Medical Center; Ginger L. Milne, Vanderbilt University; Robert Bresalier, University of Texas M.D. Anderson Cancer Center; John A. Baron, University of North Carolina
• Journal Title: Cancer Prevention Research
• Volume: Volume 8, Number 11
• Publisher: American Association for Cancer Research | 2015-11-01, Pages 1061-1068
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1940-6207.CAPR-15-0212
• Subjects: Health Sciences, Public Health; Health Sciences, Oncology; Health Sciences, Epidemiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; CHROMATOGRAPHY MASS-SPECTROMETRY; MUCOSAL PROSTAGLANDIN E-2; PGE-M LEVELS; CANCER PREVENTION; PLATELET-FUNCTION; THROMBOXANE A(2); ANTIINFLAMMATORY DRUGS; PROSTACYCLIN-SYNTHASE; RANDOMIZED-TRIAL; NITRIC-OXIDE

Abstract

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 dTxB2levels 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 dTxB2were, 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 COXdependent mechanisms may not completely explain the chemopreventive effect of aspirin on colorectal neoplasms.