Statin Use and Reduced Risk of Biliary Tract Cancers in the United Kingdom Clinical Practice Research Datalink

Abstract

Background: Potential protective effects of statins against cancers have been widely studied. However, few data exist on the association of statins with biliary tract cancers (BTCs). Methods: 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. We selected five controls who did not develop BTCs per case matched by sex, year of birth, calendar time, years of enrollment in the general practice. The history of medication use was obtained from 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. Findings: We included 3,213 BTC cases and 16,007 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0·89, 95%CI: 0·80-0·99). There was a dose-response trend with increasing number of prescriptions (Ptrend = 0·01) and cumulative dose of statins (Ptrend = 0·006). The magnitude of association was similar for statin use and risk of individual types of BTCs. Among diabetics, the reduced risk of BTCs was more pronounced among persons with statins prescribed before diabetes was diagnosed (adjusted OR=0·57, 95%CI: 0·42-0·78) than among those with statins prescribed after diabetes was diagnosed (0·83, 0·65-1·05, Pheterogeneity=0·01). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.93 (95%CI: 0·83-1·04). Interpretation: Statin use is associated with a lower risk of BTCs. If replicated in other settings, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention. Funding Statement: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. Declaration of Interests: The fifth author, Dr. Tsai, is currently an employee of the US Food and Drug Administration. The views expressed in this article are those of the authors and not necessarily those of the Food and Drug Administration. Ethics Approval Statement: The study was approved by the Independent Scientific Advisory Committee of the CPRD (proposal#17_160.R).