Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink

Objective: To evaluate the association between statin use and risk of biliary tract cancers (BTCs). Design: This is a nested case-control study based on the United Kingdom Clinical Practice Research Datalink (CPRD). We included cases diagnosed with incident primary BTCs, including cancers of the gallbladder, bile duct (i.e., both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater, and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time, and years of enrollment in the general practice using incidence density sampling. A history of prescribed medications 1 year prior to diagnosis/selection was obtained from the patient prescription records. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.Results: We included 3,118 BTC cases and 15,519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95%CI: 0.79-0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (Ptrend = 0.016) and cumulative dose of statins (Ptrend = 0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95%CI: 0.57-0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95%CI: 0.81-1.03, Pheterogeneity=0.007). Conclusion: We provide evidence that current, but not former, statin use was associated with a lower risk of BTCs compared with nonuse of statins. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.