title: Urinary metabolites of prostanoids and risk of recurrent colorectal adenomas in the Aspirin/Folate Polyp Prevention Study (AFPPS).
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 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.
authors: Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, Georgia. vfedirk@emory.edu jabaron@med.unc.edu.
authors: Veronika
authors: V
authors: Fedirko
authors: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.
authors: Patrick T
authors: PT
authors: Bradshaw
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Jane C
authors: JC
authors: Figueiredo
authors: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors: Robert S
authors: RS
authors: Sandler
authors: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors: Elizabeth L
authors: EL
authors: Barry
authors: Department of Veterans Affairs Medical Center, Denver, Colorado.
authors: Dennis J
authors: DJ
authors: Ahnen
authors: Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee.
authors: Ginger L
authors: GL
authors: Milne
authors: Department of Gastrointestinal Medicine and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Robert S
authors: RS
authors: Bresalier
authors: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina. vfedirk@emory.edu jabaron@med.unc.edu.
authors: John A
authors: JA
authors: Baron
mesh_terms: D000236:Adenoma / Q000517:prevention & control*; D000284:Administration, Oral; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D002849:Chromatography, Gas; D002853:Chromatography, Liquid; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016012:Poisson Distribution; D011453:Prostaglandins / Q000378:metabolism / Q000652:urine*
chemical_list: D011453:Prostaglandins; D005492:Folic Acid; D001241:Aspirin