Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study

Objectives: We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.

Design: Retrospective cohort study.

Setting: This research was conducted at the national level, encompassing the entire population of Sweden.

Participants: This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years.

Interventions: Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H₂RA) use.

Primary and secondary outcome measures: The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H₂RA use.

Results: Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H₂RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05).

Conclusions: Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.