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The authors compared H2 blocker users with proton pump inhibitor (PPI) users to assess for an association with colorectal cancer (CRC). Although short-term use of PPIs was not associated with CRC, long-term use may be associated. H2 blockers were not found to increase the risk.
Further studies are needed to elucidate whether a pathophysiologic mechanism exists for long-term PPI use causing CRC.
To determine whether proton pump inhibitors (PPIs) are associated with an increased risk of colorectal cancer, compared with histamine-2 receptor antagonists (H2RAs).
The United Kingdom Clinical Practice Research Datalink was used to identify initiators of PPIs and H2RA from 1990 to 2018, with follow-up until 2019. Cox proportional hazards models were fit to estimate marginal HRs and 95% CIs of colorectal cancer. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Prespecified secondary analyses assessed associations with cumulative duration, cumulative dose and time since treatment initiation. The number needed to harm was calculated at five and 10 years of follow-up.
The cohort included 1 293 749 and 292 387 initiators of PPIs and H2RAs, respectively, followed for a median duration of 4.9 years. While the use of PPIs was not associated with an overall increased risk of colorectal cancer (HR: 1.02, 95% CI 0.92 to 1.14), HRs increased with cumulative duration of PPI use (<2 years, HR: 0.93, 95% CI 0.83 to 1.04; 2-4 years, HR: 1.45, 95% CI 1.28 to 1.60; ≥4 years, HR: 1.60, 95% CI 1.42 to 1.80). Similar patterns were observed with cumulative dose and time since treatment initiation. The number needed to harm was 5343 and 792 for five and 10 years of follow-up, respectively.
While any use of PPIs was not associated with an increased risk of colorectal cancer compared with H2RAs, prolonged use may be associated with a modest increased risk of this malignancy.