Background: Long-term use of proton pump inhibitors (PPIs) use is linked to an increased risk of upper-gastrointestinal cancer.
Objectives: We aimed to assess the PPI-associated colorectal adenocarcinoma risk in a large nationwide cohort.
Methods: Swedish national registries were used to include all adults with ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding individuals with a follow-up of < 1 year. The colorectal adenocarcinoma risk in the exposed population was presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) and compared to that in the Swedish general population, stratified by age, sex, and calendar period. Subgroup analyses of SIRs included the indication, tumour location and stage, and duration after starting PPIs. The Poisson regression model was fit to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus histamine-2 receptor antagonist (H2RA) use.
Results: Overall, 754,118 maintenance PPI users were enrolled and followed up for a median duration of 5.3 years. The colorectal adenocarcinoma risk was marginally higher in maintenance PPI users than that in the general population (SIR 1.10, 95% CI= 1.06-1.13). Both men (SIR 1.13, 95% CI=1.08-1.18) and women (SIR 1.10, 95% CI=1.06-1.15) had a potentially high risk of developing colorectal adenocarcinoma compared to the general population. Participants aged 18-39 (SIR 2.79, 95% CI=1.62-4.47) and 40-49 (SIR 2.02, 95% CI=1.65-2.45) had significantly higher risk than the general population. Right-sided colorectal adenocarcinoma was associated with a higher risk than in the general population (SIR 1.26, 95% CI=1.20-1.32). Among the indications for maintenance PPI use, Helicobacter pylori infection or eradication therapy (SIR 1.29, 95% CI=1.15-1.44) and dyspepsia (SIR 1.29, 95% CI=1.16-1.42) were associated with an increased risk of colorectal adenocarcinoma. Maintenance PPI use did not differ significantly from maintenance H2RA use in terms of the risk of colorectal adenocarcinoma (IRR 1.05, 95% CI=0.87-1.26, P< 0.05).
Conclusions: Maintenance PPI use was associated with a marginally increased risk of colorectal adenocarcinoma.
