Population-based case-control study: chemoprotection of colorectal cancer with non-aspirin nonsteroidal anti-inflammatory drugs and other drugs for pain control.

BACKGROUND

Inflammation and overexpression of cyclooxygenase-2 (COX-2) have been described to play a key role in the progression from nonpathologic intestinal mucosa to colorectal cancer (CRC).

AIMS: To assess the chemoprotective effect of non-aspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) under different patterns of use in a Mediterranean population and to explore the potential effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs; chondroitin sulfate and glucosamine) and metamizole (or dipyrone), also reported to influence COX-2 activity.

METHODS

We performed a case-control study nested in a cohort extracted from the primary care database, BIFAP. From 2001 to 2014, we included 15 491 incident cases and 60 000 random controls. To estimate the association between the drugs of interest and CRC, we built logistic regression models to compute the adjusted-odds ratios (AOR) and 95% confidence intervals (CI).

RESULTS

NA-NSAIDs use was associated with a reduced risk of CRC (AOR = 0.67; 95% CI: 0.63-0.71) and increased linearly with duration of treatment (p for trend <0.001). The effect diminished upon discontinuation but persisted statistically significant up to 1 year. All individual NA-NSAIDs examined showed a decreased risk. The concomitant use of proton-pump inhibitors (PPI) had no impact on the protective effect of NA-NSAIDs; AORPPI + NSAID  = 0.64; 0.58-0.71. SYSADOA use was associated with a reduced risk (0.79; 0.69-0.90) but disappeared after the exclusion of NSAID users during the previous 1 or 3 years (0.85; 0.70-1.04 and 1.00; 0.76-1.31 respectively). Metamizole did not show a chemoprotective effect.

CONCLUSIONS

NA-NSAID use is associated with a duration-dependent risk reduction of CRC not shared by SYSADOAs or metamizole.