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Original research
Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea
  1. Seung In Seo1,2,
  2. Chan Hyuk Park3,
  3. Seng Chan You4,
  4. Jae Young Kim5,
  5. Kyung Joo Lee5,
  6. Jinseob Kim6,
  7. Yerim Kim7,
  8. Jong Jin Yoo1,
  9. Won-Woo Seo1,
  10. Hyung Seok Lee8,
  11. Woon Geon Shin1,2
  1. 1Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
  2. 2Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
  3. 3Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, South Korea
  4. 4Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
  5. 5University Industry Foundation, Hallym University, Chuncheon, South Korea
  6. 6Department of Epidemiology, School of Public Health, Seoul National University, Seoul, South Korea
  7. 7Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
  8. 8Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea
  1. Correspondence to Professor Woon Geon Shin, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea; sgun9139{at}gmail.com

Abstract

Objective The association between proton pump inhibitor (PPI) use and gastric cancer related to Helicobacter pylori eradication has not been fully investigated in geographical regions with high risk of gastric cancer. We aimed to evaluate the association between PPIs and gastric cancer in Korea.

Design This study analysed the original and common data model versions of the Korean National Health Insurance Service database from 2002 to 2013. We compared the incidence rates of gastric cancer after 1-year drug exposure, between new users of PPIs and other drugs excluding PPIs, by Cox proportional hazards model. We also analysed the incidence of gastric cancer among PPI users after H. pylori eradication.

Results The analysis included 11 741 patients in matched PPI and non-PPI cohorts after large-scale propensity score matching. During a median follow-up of 4.3 years, PPI use was associated with a 2.37-fold increased incidence of gastric cancer (PPI≥30 days vs non-PPI; 118/51 813 person-years vs 40/49 729 person-years; HR 2.37, 95% CI 1.56 to 3.68, p=0.001). The incidence rates of gastric cancer showed an increasing trend parallel to the duration of PPI use. In H. pylori-eradicated subjects, the incidence of gastric cancer was significantly associated with PPI use over 180 days compared with the non-PPI group (PPI≥180 days vs non-PPI; 30/12 470 person-years vs 9/7814 person-years; HR 2.22, 95% CI 1.05 to 4.67, p=0.036).

Conclusion PPI use was associated with gastric cancer, regardless of H. pylori eradication status. Long-term PPIs should be used with caution in high-risk regions for gastric cancer.

  • proton pump inhibition
  • gastric cancer
  • helicobacter pylori

Data availability statement

Data are available upon reasonable request. The analytic R code is available from the author WGS (e-mail, sgun9139@gmail.com).

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Data availability statement

Data are available upon reasonable request. The analytic R code is available from the author WGS (e-mail, sgun9139@gmail.com).

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Footnotes

  • Contributors SIS: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and revision of the manuscript; CHP and SCY: critical revision of the manuscript for important intellectual content; JYK and KJL: acquisition of data, analysis and interpretation of data; JK and SCY: statistical analysis; YK, JJY, WWS and HSL: technical or material support; WGS: study concept and design, obtainment of funding, revision of the manuscript and study supervision.

  • Funding This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C0481, HC19C0077).

  • Competing interests None declared.

  • Patient and public involvement statement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • 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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