Epidemiology

Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies

Abstract

Background

Studies have shown increased gastric cancer risk in users of proton pump inhibitors (PPI) and histamine-2 receptor antagonists, questioning the safety of gastric acid suppression. Therefore, we conducted a case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database and a cohort study in the UK Biobank.

Methods

In PCCIU, five controls were matched to cases diagnosed in 1999–2011, and medications were determined from GP records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. In the UK Biobank, medications were self-reported at cohort entry 2006–2010, and gastric cancer ascertained from cancer registries until 2014. Hazard ratios (HR) were calculated using Cox regression.

Results

PCCIU contained 1119 cases and 5394 controls. UK Biobank contained 250 cases in 471,779 participants. PPI users had a higher gastric cancer risk in PCCIU and UK Biobank when applying a 1-year lag (adjusted OR = 1.49, 95% CI 1.24, 1.80; adjusted HR = 1.28, 95% CI 0.86, 1.90, respectively), but these associations were attenuated when using a 2-year lag (adjusted OR = 1.13, 95% CI 0.91, 1.40; adjusted HR = 1.15, 95% CI 0.73, 1.82, respectively).

Conclusions

Overall, we observed little consistent evidence of an increased risk of gastric cancer with PPI use.

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Acknowledgements

Access to UK Biobank data was approved and facilitated by the UK Biobank (application number: 34374). Access to Primary Care Clinical Informatics Unit (PCCIU) data was approved and facilitated by the PCCIU Research team, University of Aberdeen. Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship awarded to ÚCMcM.

Author information

Affiliations

Authors

Contributions

Study concept and design: Lee A.J., Cardwell C.R., Iversen L. and Murchie P. Data acquisition: Lee A.J., Cardwell C.R., Iversen L., Murchie P. and McMenamin U.C. Funding for various aspects of study: Lee A.J., Cardwell C.R., Iversen L., Murchie P., Liu P. and McMenamin U.C. Statistical analysis: Cardwell C.R. and Liu P. Data interpretation: Cardwell C.R., Liu P., Johnston B.T., Iversen L., Murchie P., Vissers P.A.J. and McMenamin U.C.. Study supervision: Cardwell C.R. Critical review of the paper for important intellectual content: Cardwell C.R., Murchie P., Johnston B.T., Iversen L. and Vissers P.A.J. Paper writing: Cardwell C.R. and Liu P. Final approval: all authors.

Corresponding author

Correspondence to Peipei Liu.

Ethics declarations

Ethics approval and consent to participate

Ethical approval for the PCCIU data was supplied by the Queen’s University Belfast, School of Medicine and Dentistry and Biomedical Sciences Research Ethics Committee (reference number: 15.43). The UK Biobank has ethical approval from the North West Multi-Centre Research Ethics Committee. All UK Biobank participants provided written informed consent. The study was performed in accordance with the Declaration of Helsinki.

Consent to publish

Not applicable.

Data availability

The UK Biobank data (https://www.ukbiobank.ac.uk/) and PCCIU data (https://www.abdn.ac.uk/iahs/research/primary-care/pcciur/) are available, following the access procedures, for researchers to access to conduct health-related research in the public interest.

Competing interests

The authors declare no competing interests.

Funding information

Access to the UK Biobank was funded by a Cancer Research UK Population Research Postdoctoral Fellowship awarded to ÚCMcM. Liu P. was supported by a joint scholarship from Queen’s University Belfast and the Chinese Scholarship Council (201708060458).

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Liu, P., McMenamin, Ú.C., Johnston, B.T. et al. Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies. Br J Cancer 123, 307–315 (2020). https://doi.org/10.1038/s41416-020-0860-4

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