Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma

BACKGROUND: Statins have been proven to be cytotoxic to human cholangiocarcinoma cells by inhibiting cell division and inducing apoptosis. We aimed to determine the effect of statin use on the risk of cancer development and survival in patients with extrahepatic cholangiocarcinoma (ECC) including perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA). METHODS: 394 patients with ECC and hyperlipidemia who received care at Mayo Clinic Rochester between 2005 and 2015 were matched by age, sex, race, ethnicity and residency to 788 controls with hyperlipidemia. Clinical and outcome data was abstracted. The odds ratios for risk and hazard ratios for outcomes were calculated. RESULTS: The mean age and standard deviation (SD) for cases and controls was 65.6 years (13.8). The number of statin users in cases and controls were 73 (19%) and 403 (51%), respectively. Hepatitis C virus infection (OR=15.84, 95% CI 4.06-61.87; p<0.001) was the most significant risk factor for pCCA followed by inflammatory bowel disease and cirrhosis, whereas other liver diseases including biliary stone disease (OR=4.06, 2.24-7.36; p<0.001) was the only significant risk factor for dCCA. Statin use was associated with significantly reduced risk for all ECC (OR=0.22, 0.16-029) as well as for the subtypes pCCA (OR=0.3, 0.21-0.41) and dCCA (OR=0.06, 0.03-0.14) all p<0.0001. Moderate intensity dosage was found to decrease the risk of ECC (OR=0.48, 0.34-0.67, p<0.001). Comparing statin ever users to non-users, dCCA patients who used statins had significantly overall better survival (HR=0.53, 0.29-0.97, p=0.04). CONCLUSION: This case-control study suggests that statins decrease the risk of extrahepatic cholangiocarcinoma and may improve survival in patients with dCCA. Additional validation studies are warranted.