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

Abstract

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 longterm 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,, 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.

Does the Use of Proton Pump Inhibitors Increase the Risk of Pancreatic Cancer? A Systematic Review and Meta-Analysis of Epidemiologic Studies

“…They were published between 2012 and 2020 in six countries. Three studies were conducted in the UK [ 36 , 37 , 41 ], two in the USA [ 32 , 42 ], two in Taiwan [ 30 , 33 ], one in Korea [ 35 ], one in Denmark [ 34 ] and one in Sweden [ 43 ]. The follow-up duration was between 5 and 20 years.…”

“…The diagnosis of pancreatic cancer was based on the ICD codes in six studies [ 30 , 32 , 33 , 35 , 42 , 43 ], medical record code in two studies [ 36 , 37 ], and histological verification of PDA in two studies [ 34 , 41 ]. Stratified analysis according to the PPI dose and duration was performed in five studies [ 32 , 33 , 34 , 35 , 36 ] and in the five other studies [ 32 , 33 , 36 , 37 , 43 ], respectively, although they all used a different cutoff value of dose and duration. In six studies, pancreatic cancer cases that developed within 1 or 2 years after PPI introduction were excluded because PPI was probably used to help in treating and diagnosing cancer-associated symptoms [ 30 , 32 , 33 , 34 , 35 , 36 ].…”

Research Progress of Pancreas-Related Microorganisms and Pancreatic Cancer

“…It is suggested that the common bile duct stent may affect the duodenal microbiome. Many clinical factors such as proton pump inhibitors may affect the composition of colonized microbiome in the pancreas and increase the risk of pancreatic cancer ( 43 , 44 ).…”

Problematiske protonpumpehemmere

“…Selv om observasjonsstudier har vist til dels motstridende resultater, har nyere registerstudier og metaanalyser vist at langvarig bruk av protonpumpehemmere dobler risikoen for kreft i pankreas og magesekk. Enkelte studier har vist økt risiko for kolorektalkreft (4)(5)(6).…”