Proton pump inhibitors and odds of cholangiocarcinoma: A retrospective case-control study

Background & Aims Proton pump inhibitors (PPIs) have been reported to be associated with cholangitis and might possibly be carcinogenic. However, few studies have been conducted to investigate the association of PPIs with cholangiocarcinoma (CCA). Thus, a hospital-based case-control study was carried out in China to explore the association between PPIs and CCA. Methods In this study, 1468 CCA cases (826 intrahepatic cholangiocarcinoma (ICC) and 642 extrahepatic cholangiocarcinoma (ECC)) were included, which were observed at Beijing Friendship Hospital, from February 2002 to October 2018. We retrospectively extracted PPI use and other possible risk factors from clinical records, followed by an investigation of the relationship with CCA via calculation of odds ratios (ORs), adjusted odds ratios (AORs), and 95% confidence intervals (CIs) using logistic regression analysis. Results PPIs were used by 135 (9.2%) CCA cases and 173 (5.9%) controls. We found that PPI use was associated with a 1.61-fold elevated CCA odds (P < .001) (AOR = 1.61, 95% CI = 1.28-2.05; P < .001). After stratification by CCA subtypes, the AORs of PPIs were consistent for both CCA subtypes, with ORs of 1.36 (AOR = 1.36, 95% CI = 1.02-1.83; P = .003) and 1.95 (AOR = 1.95, 95% CI = 1.46-2.62; P < .001) for ICC and ECC respectively. Our results also showed that PPI use was slightly linked to the odds of CCA in a dose-dependent manner. Conclusion PPI use was correlated with a significant 61% increased odds of CCA, particularly in the ECC. However, the retrospective design and observational nature cannot establish causation. Larger scale, multi-centre prospective studies are required for further validation.