Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing

Br J Cancer. 1999 Sep;81(1):62-8. doi: 10.1038/sj.bjc.6690651.


Epidemiological studies show that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer incidence. We measured the rate ratio for colorectal adenocarcinoma according to dosage and the timing of exposure by means of a case-control study, nested in a non-concurrent cohort linkage study, using the population of beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970 as the source population. Four controls per case, matched on age and gender and alive when the case was diagnosed, were randomly selected. Dispensing rates, calculated over successive time periods, characterized NSAID exposure. We accrued 3844 cases of colon cancer and 1971 cases of rectal cancer. For colon cancer a significant trend towards a decreasing rate ratio was associated with increasing exposure during the 6 months preceding diagnosis (P-trend = 0.002). For both cancers, significant trends were associated with exposure 11-15 years before diagnosis (colon: P-trend = 0.01; rectum: P-trend = 0.0001). At the highest exposure levels the rate ratio for colon cancer was 0.57 (95% confidence interval (CI) 0.36-0.89); for rectal cancer it was 0.26 (95% CI 0.11-0.61). No protection was associated with exposure during other periods. The timing of NSAID use must be considered in planning intervention trials to prevent colorectal cancer. There may be a 10-year delay before any preventive effect will appear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anticarcinogenic Agents / administration & dosage*
  • Anticarcinogenic Agents / therapeutic use
  • Case-Control Studies
  • Cohort Studies
  • Colonic Neoplasms / epidemiology
  • Colonic Neoplasms / prevention & control*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Rectal Neoplasms / epidemiology
  • Rectal Neoplasms / prevention & control*
  • Risk Factors
  • Saskatchewan / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents