Effect of aspirin on prostaglandin E2 formation and transforming growth factor alpha expression in human rectal mucosa from individuals with a history of adenomatous polyps of the colon

Abstract

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 study 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 E2 (PGE2) formation and transforming growth factor alpha (TGF-alpha) expression] in normal-appearing rectal mucosa from individuals with a history of adenomatous polyps. Rectal biopsies were obtained by flexible sigmoidoscopy at three sequential time points: (a) after a 1-month placebo run-in period (baseline), (b) after 3 months of ingesting 81 mg of aspirin (as a single tablet) once per day, and (c) after 3 months of ingesting a placebo tablet once per day (washout period). Daily aspirin significantly suppressed PGE2 formation, but this significant suppression was completely reversed when aspirin was withdrawn. The extent of TGF-alpha staining in rectal crypts was also reduced significantly (P = 0.039) by daily aspirin. After a 3-month placebo-washout period, however, the mean extent of TGF-alpha staining was not significantly different from either baseline or the aspirin time point. Thus, 81 mg of aspirin daily significantly reduced rectal mucosal PGE2 formation and TGF-alpha expression in patients with a history of adenomatous polyps. These putative surrogate end point biomarkers may be useful intermediate end points in future colorectal cancer chemoprevention trials.