Association between proton pump inhibitor use and the risk of pancreatic cancer: A Korean nationwide cohort study

Proton pump inhibitor (PPI) therapy causes hypergastrinemia, which could promote the development and progression of pancreatic cancer. Accordingly, this study aimed to investigate the association between PPI exposure and the risk of pancreatic cancer. We conducted a twelve-year longitudinal population-based study (2002-2013) using the Korean National Health Insurance Corporation claims database merged with national health examination data. The study cohort included 453,655 cancer-free individuals in January 2007 (index date). Incident pancreatic cancer was assessed throughout follow up until December 2013. The exposure to PPIs before the index date was assessed using a standardized Defined Daily Dose (DDD) system. We calculated the hazard ratios (HRs) and their 95% confidence intervals (CIs) for pancreatic cancer risk associated with cumulative PPI use using Cox proportional hazard regression models. There were 3,086 cases of pancreatic cancer during the period of 2,920,000 person-years. PPI users exceeding 60 DDDs were at a higher risk of pancreatic cancer compared with non-users (HR, 1.34; 95% CI, 1.04-1.72). Subgroup analyses revealed that a significant association existed between PPI use and pancreatic cancer in low risk groups including individuals who were female, engaged in healthy lifestyle habits, and had no history of diabetes or chronic pancreatitis. Exposure to PPI appears to increase the risk of pancreatic cancer, independent of conventional risk factors.