Colonic mucosal prostaglandin e2 and cyclooxygenase expression before and after low aspirin doses in subjects at high risk or at normal risk for colorectal cancer1, 2

Koyamangalath Krishnan, Mack T. Ruffin, Daniel Normolle, Imad Shureiqi, Kimberley Burney, Joann Bailey, Marc Peters-Golden, Cheryl L. Rock, C. Richard Boland, Dean E. Brenner

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Development of potential cancer chemopreventive drugs involves the systematic evaluation of these drugs in preliminary Phase I and II studies in human beings to identify the optimal drug dose, drug toxicity, and surrogate end point biomarker modulation. Objectives: We tested the hypothesis that aspirin, at a single, once-daily 81-mg dose, will reduce colonic mucosal concentration of prostaglandin estradiol (E2) in individuals at high risk for colorectal cancer development similar to our prior observations in a young normal-risk population. Methods: Aspirin was administered at a dose of 81 mg once daily for 28 days in a cohort of 92 matched high-risk and normal-risk colorectal cancer subjects. Prostaglandin E2 and cyclooxygenase expression were assayed from distal sigmoid biopsies from all of the subjects before and after treatment. Results: The mean prostaglandin E2 for normal-risk subjects before aspirin treatment was 11.3 ± 1.7 pg/μg (mean ± SE) tissue protein and after aspirin treatment was 4.9 ± 0.91 pg/μg tissue protein (P & 0.0001). In high-risk subjects, mean pretreatment prostaglandin E2 was 14.4 ± 1.7 pg/μg tissue protein and after aspirin treatment was 4.7 ± 0.70 pg/μg tissue protein (P & 0.0001). Aspirin treatment did not alter cyclooxygenase-1 protein expression. Conclusions: Aspirin treatment at a dose of 81 mg reduces colorectal mucosal prostaglandin E2 concentration after 28 daily doses. Risk for colorectal carcinoma did not modify colorectal mucosal baseline or post-aspirin prostaglandin E2, or cyclooxygenase expression. Colorectal mucosal prostaglandin concentration may be used as a "drug-effect surrogate biomarker," that is, a surrogate to assess sufficient delivery and tissue effect of a chemopreventive agent.

Original languageEnglish (US)
Pages (from-to)447-453
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume10
Issue number5
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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