Aspirin and Statin Use and the Risk of Gallbladder Cancer

SIMPLE SUMMARY: The effects of aspirin on various gastrointestinal cancers have been extensively studied, but the potential protective effect of aspirin and statins on the prevention of gallbladder cancer (GBC) has not been adequately evaluated. The anticancer effect of aspirin has been attributed to direct inhibition of cyclooxygenase (COX)-2. Interestingly, increased expression of COX-2 has been documented in GBC. Hence, we hypothesized that aspirin could potentially have a preventive role in decreasing the risk of GBC. In this study, we demonstrated that the use of aspirin either alone or in combination with statins was associated with a strong reduction in risk of GBC. ABSTRACT: Aspirin and statin drugs have been associated with reduced risk of several gastrointestinal cancers, but their association with gallbladder cancer (GBC) has not been well established. We evaluated the association of aspirin and statins with the risk of GBC. Patients with GBC managed at Mayo Clinic between 2000 and 2019 were matched 1:2 with a general patient pool by age and sex. Univariable and multivariable logistic regression models were used to assess associations between GBC and aspirin or statin use. The analysis included 795 cases and 1590 controls, with a median age of 67 years. Aspirin or statin use alone or in combination was higher in controls (p < 0.001). Univariate analysis showed that the use of aspirin [odds ratio (OR): 0.11; 95%CI: 0.08–0.15] or statins (OR: 0.29; 95%CI: 0.20–0.40) and their combined use (OR: 0.18; 95%CI: 0.13–0.24) was associated with lower risk of GBC. Multivariable analysis revealed that aspirin (OR: 0.12; 95%CI: 0.09–0.16) and combined statins and aspirin (OR: 0.46; 95%CI: 0.31–0.67) were associated with lower risk of GBC. Aspirin alone or in combination with statins is associated with a strongly reduced risk of GBC. Further prospective studies are needed to confirm these results and to elucidate their mechanisms.