Abstract
PurposeProton 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.MethodsWe 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.ResultsThere 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.ConclusionExposure to PPI appears to increase the risk of pancreatic cancer, independent of conventional risk factors.
Highlights
Since their first introduction in the late 1980s, proton pump inhibitors (PPIs) have been widely used in clinical practice because they are generally well tolerated and highly effective [1]
Exposure to PPI appears to increase the risk of pancreatic cancer, independent of conventional risk factors
Hypergastrinemia [4, 5] and hyperplasia of enterochromaffin-like cells [4, 6, 7] are commonly observed among long-term PPI users
Summary
Since their first introduction in the late 1980s, proton pump inhibitors (PPIs) have been widely used in clinical practice because they are generally well tolerated and highly effective [1]. Healthcare providers often prescribe PPIs for prolonged periods, sometimes lifetime of the patient, even in the absence of appropriate indications [2]. Similar to other pharmacologic agents, there is a growing concern regarding the potential adverse effects of long-term PPI exposure [3]. Tumorigenesis is one of the major concerns among long-term PPI users. Hypergastrinemia [4, 5] and hyperplasia of enterochromaffin-like cells [4, 6, 7] are commonly observed among long-term PPI users. Gastrin receptor antagonists prevent the growth of pancreatic cancer cells [8], and a gastrin inhibitor or antibody prolong survival in patients with pancreatic cancer [11, 12]
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