Objective To determine whether proton pump inhibitors (PPIs) are associated with an increased risk of colorectal cancer, compared with histamine-2 receptor antagonists (H2RAs).
Design 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.
Results 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.
Conclusion 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.
- colorectal cancer
- acid-related diseases
Data availability statement
No data are available. No additional data available.
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Contributors All authors conceived and designed the study. LA acquired the data. DA and LA did the statistical analyses. MES and SS provided statistical expertise. All authors analysed and interpreted the data. EGM and ANB provided clinical expertise. DA wrote the manuscript, and all authors critically revised the manuscript. LA supervised the study and is the guarantor. All authors approved the final version of the manuscript and agree to be accountable for the accuracy of the work.
Competing interests SS participated in advisory meetings or as a guest speaker for Atara Biotherapeutics, Boehringer-Ingelheim, Bristol-Myers-Squibb, Merck and Pfizer, all unrelated to this study. LA served as a consultant for Janssen and Pfizer for work unrelated to this study. The other authors have no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review Not commissioned; externally peer reviewed.
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