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Original research
Proton pump inhibitors and risk of gastric cancer: population-based cohort study
  1. Devin Abrahami1,2,
  2. Emily Gibson McDonald3,4,
  3. Mireille E Schnitzer1,5,
  4. Alan N Barkun1,6,
  5. Samy Suissa1,2,7,
  6. Laurent Azoulay1,2,8
  1. 1Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
  2. 2Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
  3. 3Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
  4. 4Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada
  5. 5Faculty of Pharmacy and the Department of Social and Preventive Medicine, Universite de Montreal, Montreal, Quebec, Canada
  6. 6Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
  7. 7Department of Medicine, McGill University, Montreal, Quebec, Canada
  8. 8Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada
  1. Correspondence to Dr Laurent Azoulay, Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada; laurent.azoulay{at}mcgill.ca

Abstract

Objective To determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs).

Design Using the UK Clinical Practice Research Datalink, we conducted a population-based cohort study using a new-user active comparator design. From 1 January 1990 to 30 April 2018, we identified 973 281 new users of PPIs and 193 306 new users of H2RAs. Cox proportional hazards models were fit to estimate HRs and 95% CIs of gastric cancer, and the number needed to harm was estimated using the Kaplan-Meier method. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Secondary analyses assessed duration and dose–response associations.

Results After a median follow-up of 5.0 years, the use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2RAs (HR 1.45, 95% CI 1.06 to 1.98). The number needed to harm was 2121 and 1191 for five and 10 years after treatment initiation, respectively. The HRs increased with cumulative duration, cumulative omeprazole equivalents and time since treatment initiation. The results were consistent across several sensitivity analyses.

Conclusion The findings of this large population-based cohort study indicate that the use of PPIs is associated with an increased risk of gastric cancer compared with the use of H2RAs, although the absolute risk remains low.

  • epidemiology
  • gastric cancer
  • acid-related diseases

Data availability statement

No data are available. No additional data available.

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Data availability statement

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Footnotes

  • 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. All authors approved the final version of the manuscript and agree to be accountable for the accuracy of the work. LA supervised the study and is the guarantor.

  • Funding Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328).

  • 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 3 years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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