Statins associate with lower risk of biliary tract cancers: A systematic review and meta-analysis.

Background: Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs.

Methods: PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random-effects model.

Results: Eight observational studies (3 cohort and 5 case-control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0-71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51-0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38-0.94) and GBC was 0.78 (95% CI: 0.68-0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66-1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69-0.88) and 0.70 (95% CI: 0.61-0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non-steroidal anti-inflammatory drugs (aRR: 0.80, 95% CI: 0.72-0.89) and metformin (aRR: 0.80, 95% CI: 0.72-0.90).

Conclusions: Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC.