Objective To evaluate the association between statin use and risk of biliary tract cancers (BTC).
Design This is a nested case–control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, 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 enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.
Results We included 3118 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 to 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 a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007).
Conclusion Compared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. 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.
- biliary duct carcinoma
- gall bladder cancer
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Contributors ZL was involved in the study design, analysis and interpretation of data and writing the manuscript. RA, KAM, LAA, HTT, YZ, SMM and SMG were involved in conception of the study, interpretation of data and revision of the manuscript. BZ was involved in data analysis, interpretation of data and revision of the manuscript. JK was involved in conception of the study, study design, interpretation of data and writing the manuscript. All authors revised the article critically for important intellectual content and gave final approval of the version to be published.
Funding Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.
Disclaimer The funders had no role in the conduct of this research. The views expressed in this article are those of the authors and not necessarily those of the US Food and Drug Administration.
Competing interests HTT is currently an employee of the US Food and Drug Administration.
Patient consent Not required.
Ethics approval Independent Scientific Advisory Committee of the CPRD (proposal number 17_160.R).
Provenance and peer review Not commissioned; externally peer reviewed.
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