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

Epidemiological studies show that non-steroidal anti-inflammatory drugs (NS AIDs) reduce colorectal cancer incidence. We measured the rate ratio for co lorectal adenocarcinoma according to dosage and the timing of exposure by m eans of a case-control study, nested in a non-concurrent cohort linkage stu dy, using the population of beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970 as the sou rce population. Four controls per case, matched on age and gender and alive when the case was diagnosed, were randomly selected. Dispensing rates, cal culated over successive time periods, characterized NSAID exposure. We accr ued 3844 cases of colon cancer and 1971 cases of rectal cancer. For colon c ancer a significant trend towards a decreasing rate ratio was associated wi th increasing exposure during the 6 months preceding diagnosis (P-trend = 0 .002), For both cancers, significant trends were associated with exposure 1 1-15 years before diagnosis (colon: P-trend = 0.01; rectum: P-trend = 0.000 1), 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 (9 5% CI 0.11-0.61), No protection was associated with exposure during other p eriods. The timing of NSAID use must be considered in planning intervention trials to prevent colorectal cancer. There may be a 10-year delay before a ny preventive effect will appear.