Cancer
Use of Non-steroidal Anti-inflammatory Drugs, Aspirin, Ibuprofen, and Acetaminophen in Relation to Biliary Tract Cancers in the Biliary Tract Cancers Pooling Project (BiTCaPP) Ilona Argirion* Ilona Argirion Crystal Najib Katherine McGlynn Peter Campbell
Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to reduce the risk of several cancers, leading to their proposed use as chemopreventive agents; nevertheless, their relationship with biliary tract cancers (BTCs) remains to be fully elucidated.
Methods: Data from thirteen prospective studies in the Biliary Tract Cancers Pooling Project (BiTCaPP) were harmonized to investigate the association between NSAIDs (aspirin and ibuprofen), acetaminophen, and BTCs. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression after adjustment for sex, race, education, smoking, alcohol use, body mass index, and cardiovascular disease. Sensitivity analyses were conducted to assess the role of duration and intensity of use, presence of gallstones, and cholecystectomy on the observed associations.
Results: During 19,036,644 person-years of follow up, 494 gallbladder cancer (GBC), 339 intrahepatic bile duct cancer (IHBDC), 499 extrahepatic bile duct cancer (EHBDC), and 291 ampulla of Vater cancer (AVC) cases occurred. NSAIDs were inversely associated with IHBDC (HR=0.57 [95%CI: 0.44-0.73]) and EHBDC (HR=0.76 [95%CI: 0.62-0.94]); similar results were found for aspirin (HRIHBDC=0.58 [95%CI: 0.45-0.75]; HREHBDC=0.80 [95%CI: 0.64-0.98]). Ibuprofen use was inversely associated with IHBDC (HR=0.71 [95%CI: 0.52-0.97]) and AVC (HR=0.61 [95%CI: 0.43-0.86]). Increasing intensity of NSAID use was associated with decreased EHBDC risk (ptrend=0.04), and increased intensity of aspirin use was associated with decreased IHBDC risk (ptrend=0.02), while increasing intensity of acetaminophen use was associated with increased IHBDC and EHBDC risk (ptrend=0.003 and 0.02, respectively). Results did not vary by cholecystectomy or gallstone status.
Conclusion: NSAIDs mitigate chronic inflammation and could protect against IHBDC and EHBDC. Conversely, acetaminophen use may increase the risk of IHBDC and EHBDC.