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Risk of gastric cancer among long-term proton pump inhibitor users: a population-based cohort study

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Abstract

Purpose

To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk.

Methods

We searched the 2009–2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009–2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)–matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose–response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users.

Results

After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8–9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85–0.96) and 0.81 (0.76–0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06–1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25–4.60)). GC–related mortality did not differ significantly between PPI users and non-users.

Conclusion

In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose–response relationship.

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Availability of data and materials

Due to the regulations of the Korean National Health Insurance Sharing Services, there is a limitation to the access of the database. Approval from the institution is necessary to get access to the closed server for a limited time. All relevant data are within the manuscript and its supporting information files.

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Funding

This study was funded by a grant from the Korea Health Technology Research and Development Project (grant no. HC19C0060).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea

    Jong Wook Kim

  2. Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea

    Hye-Kyung Jung & Jitaek Hong

  3. Institute of Health & Environment, Seoul National University, Seoul, Korea

    Bora Lee

  4. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

    Cheol Min Shin

  5. Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea

    Eun Jeong Gong

  6. Department of Internal Medicine, Yonsei University Gangnam Severance Hospital, Seoul, Korea

    Young Hoon Youn

  7. Department of Gastroenterology, Ajou University School of Medicine & Graduate School of Medicine, Suwon, Korea

    Kwang Jae Lee

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Contributions

JWK: analysis and interpretation of data, drafting of the manuscript, and revision of the manuscript; BL: statistical analysis and interpretation of data; HKJ: study concept and design, acquisition of data, obtainment of funding; CMS: study concept and design, critical revision of the manuscript; EJG, JH, YHY, and KJL: critical revision of the manuscript and study supervision.

Corresponding author

Correspondence to Hye-Kyung Jung.

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Ethical approval

The study protocol was approved by the institutional review board of Ewha Women’s University Hospital (IRB number EUMC 2020–07-028).

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The authors declare no competing interests.

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Kim, J.W., Jung, HK., Lee, B. et al. Risk of gastric cancer among long-term proton pump inhibitor users: a population-based cohort study. Eur J Clin Pharmacol 79, 1699–1708 (2023). https://doi.org/10.1007/s00228-023-03580-7

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  • DOI: https://doi.org/10.1007/s00228-023-03580-7

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