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

## TL;DR

Long-term use of proton pump inhibitors may slightly increase the risk of colorectal cancer, especially in younger people and for right-sided tumors.

## Contribution

This study provides population-level evidence on the association between long-term PPI use and colorectal cancer risk in Sweden.

## Key findings

- Maintenance PPI users had a 10% higher risk of colorectal cancer compared to the general population.
- Younger users (18–49 years) showed significantly higher cancer risks than the general population.
- Right-sided colorectal cancer risk was elevated, but no significant difference was found between PPI and H2RA users.

## Abstract

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.

Retrospective cohort study.

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

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.

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

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.

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).

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