Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors for Primary Prevention of Colorectal Cancer: A Systematic Review Prepared for the U.S. Preventive Services Task Force

6 March 2007 | Volume 146 Issue 5 | Pages 376-389

Purpose: To examine the benefits and harms of nonaspirin (non-ASA) nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX-2) inhibitors for the prevention of colorectal cancer (CRC) and adenoma.

Data Sources: MEDLINE (1966 to 2006), EMBASE (1980 to 2006), Cochrane Central Register of Controlled Trials, Cochrane Collaboration's registry of clinical trials, Cochrane Database of Systematic Reviews.

Study Selection: Randomized, controlled trials and case–control and cohort studies of the effectiveness of NSAIDs for the prevention of CRC and colorectal adenoma were identified by multilevel screening by 2 independent reviewers. Systematic reviews of harms were sought.

Data Extraction: Data abstraction, checking, and quality assessment were completed in duplicate.

Data Synthesis: A single cohort study showed no effect of non-ASA NSAIDs on death due to CRC. Colorectal cancer incidence was reduced with non-ASA NSAIDs in cohort studies (relative risk, 0.61 [95% CI, 0.48 to 0.77]) and case–control studies (relative risk, 0.70 [CI, 0.63 to 0.78]). Colorectal adenoma incidence was also reduced with non-ASA NSAID use in cohort studies (relative risk, 0.64 [CI, 0.48 to 0.85]) and case–control studies (relative risk, 0.54 [CI, 0.4 to 0.74]) and by COX-2 inhibitors in randomized, controlled trials (relative risk, 0.72 [CI, 0.68 to 0.77]). The ulcer complication rate associated with non-ASA NSAIDs is 1.5% per year. Compared with non-ASA NSAIDs, COX-2 inhibitors reduce this risk but, in multiyear use, have a higher ulcer complication rate than placebo. Cyclooxygenase-2 inhibitors and nonnaproxen NSAIDs increase the risk for serious cardiovascular events (relative risk, 1.86 [CI, 1.33 to 2.59] for COX-2 inhibitors vs. placebo).

Limitations: Heterogeneity in the dose, duration and frequency of use necessitated careful grouping for analysis.

Conclusions: Cyclooxygenase-2 inhibitors and NSAIDs reduce the incidence of colonic adenomas. Nonsteroidal anti-inflammatory drugs also reduce the incidence of CRC. However, these agents are associated with important cardiovascular events and gastrointestinal harms. The balance of benefits to risk does not favor chemoprevention in average-risk individuals.

Author and Article Information

From University of Calgary, Calgary, Alberta, Canada, and Chalmers Research Group, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, and Carleton University, Ottawa, Ontario, Canada.

Acknowledgments: The investigators thank Mary White, ScD, Chief Epidemiology and Applied Research Branch (CDC); Patrik Johansson, MD, Medical Officer (AHRQ); Therese Miller, DrPH, Task Order Officer (AHRQ); Janelle Guirguis-Blake, MD, USPSTF Program Director; and Elizabeth A. Edgerton, MD, MPH, Director of Clinical Prevention. They also thank members of the USPSTF who served as leads for the project: Ned Calonge, MD, MPH; Michael LeFevre, MD, MSPH; Carol Loveland-Cherry, PhD, RN; and Al Siu, MD, MSPH. They thank Nav Saloojee, MD, for helping in the selection of relevant reports; Tiffany Richards for assisting with the evidence tables; Raymond Daniel for retrieving the full reports; Chantelle Garritty for helping to coordinate the process; and Isabella Steffensen and Christine Murray for dedicating many long hours to editing the report and its appendix tables.

Grant Support: By the Centers for Disease Control and Prevention for the Agency for Healthcare Research and Quality and the U.S. Preventive Services Task Force.

Potential Financial Conflicts of Interest: Consultancies: A. Rostom (Novartis); Honoraria: A. Rostom (Novartis); Grants received: A. Rostom (Agency for Healthcare Research and Quality/U.S. Preventive Services Task Force), C. Dubé (Agency for Healthcare Research and Quality/U.S. Preventive Services Task Force).

Requests for Single Reprints: Alaa Rostom, MD, MSc, Division of Gastroenterology, Health Science Centre, 3330 Hospital Drive North West, Calgary, Alberta T2N 4N1, Canada; e-mail, arostom{at}ucalgary.ca.

Current Author Addresses: Drs. Dubé and Rostom: Division of Gastroenterology, University of Calgary Medical Clinic, 3330 Hospital Drive North West, #G176, Calgary, Alberta, T2N 1N4 Canada.

Drs. Lewin, Tsertsvadze, Barrowman, Sampson, and Moher: Chalmers Research Group, CHEO Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.

Dr. Code: Division of Internal Medicine, The Ottawa Hospital—Civic Site, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada.

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