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Background  The long-term safety of proton pump inhibitors (PPIs) is increasingly questioned. The aim of our study was to assess the risk of pancreatic cancer among long-term PPI users in Sweden.    Methods  This population-based nationwide Swedish cohort study including 796,492 adult long-term PPI users has been used to calculate the standardized incidence rate ratios (SIRs) and 95% confidence intervals (CI) for pancreatic cancer, stratifying by indications of use, age, sex, and duration of use. The risk among all 20,210 long-term H2-receptor antagonist users was assessed as comparison.    Results  Pancreatic cancer was found in 1733 long-term PPI users, and 25 H2-receptor antagonist users. For PPI users, the risk of pancreatic cancer was increased overall (SIRs = 2.22; 95% CI 2.12–2.32) and in all subgroup analyses, with the highest risk among PPI-users younger than 40 years (SIR = 8.90, 95% CI 4.26–16.37), and among individuals with a history of  Helicobacter pylori  (SIR = 2.99, 95% CI 2.54–3.49). After the first year after enrolment (during which PPI use may be because of early symptoms of pancreatic cancer), the risk remained increased over time, with SIR = 1.57 (95% CI 1.38–1.76) after 5 years. No associations were found for H2-receptor antagonists (SIR = 1.02, 95% CI 0.66–1.51).    Conclusions  This large study showed an increased risk of pancreatic cancer in long-term users of PPIs in Sweden, in particular among the youngest users.

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden