Effect of aspirin on prostaglandin E-2 formation and transforming growth factor a expression in human rectal mucosa from individuals with a history of adenomatous polyps of the colon

Colorectal cancer is the second-most frequent cause of cancer mortality in the United States. Human epidemiology and laboratory studies indicate that aspirin may be an effective colorectal cancer chemopreventive agent. This s tudy was designed to determine whether treatment with 81 mg of aspirin per day for 3 months would alter two putative surrogate end point biomarkers of chemoprevention of colorectal cancer [i.e,, mucosal prostaglandin E-2 (PGE (2)) formation and transforming growth factor alpha (TGF-alpha) expression] in normal-appearing rectal mucosa from individuals with a history of adeno matous polyps. Rectal biopsies were obtained by flexible sigmoidoscopy at t hree sequential time points: (a) after a 1-month placebo run-in period (bas eline), (b) after 3 months of ingesting 81 mg of aspirin (as a single table t) once per day, and (c) after 3 months of ingesting a placebo tablet once per day (washout period). Daily aspirin significantly suppressed PGE(2) for mation, but this significant suppression was completely reversed when aspir in was withdrawn. The extent of TGF-alpha staining in rectal crypts was als o reduced significantly (P = 0.039) by daily aspirin. After a 3-month place bo-washout period, however, the mean extent of TGF-alpha staining was not s ignificantly different from either baseline or the aspirin time point. Thus , 81 mg of aspirin daily significantly reduced rectal mucosal PGE(2) format ion and TGF-alpha expression in patients with a history of adenomatous poly ps, These putative surrogate end point biomarkers may be useful intermediat e end points in future colorectal cancer chemoprevention trials.