title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Data abstraction, checking, and quality assessment were completed in duplicate.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Calgary, Calgary, Alberta, Canada. arostom@ucalgary.ca
authors.forename: Alaa
authors.initials: A
authors.lastname: Rostom
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubé
authors.forename: Gabriela
authors.initials: G
authors.lastname: Lewin
authors.forename: Alexander
authors.initials: A
authors.lastname: Tsertsvadze
authors.forename: Nicholas
authors.initials: N
authors.lastname: Barrowman
authors.forename: Catherine
authors.initials: C
authors.lastname: Code
authors.forename: Margaret
authors.initials: M
authors.lastname: Sampson
authors.forename: David
authors.initials: D
authors.lastname: Moher
mesh_terms: D000236:Adenoma / Q000517:prevention & control; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D003111:Colonic Polyps / Q000517:prevention & control; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D008297:Male; D011322:Primary Prevention; D014481:United States / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors