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Original Article
Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study
  1. Ka Shing Cheung1,
  2. Esther W Chan2,
  3. Angel Y S Wong2,
  4. Lijia Chen1,
  5. Ian C K Wong2,3,
  6. Wai Keung Leung1
  1. 1Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
  2. 2Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Hong Kong
  3. 3UCL School of Pharmacy, University College London, London, UK
  1. Correspondence to Dr Wai Keung Leung, Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong; waikleung{at}


Objective Proton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy.

Designs This study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure.

Result Among the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for 1 year, ≥2 years and 3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years.

Conclusion Long-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.

  • stomach cancer
  • gastric adenocarcinoma
  • Helicobacterpylori

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  • Contributors KSC, ICKW and WKL were involved with the study concept and design, analysis and interpretation of data, drafting of manuscript and approval of the final version of the manuscript. EWC, AYSW and LC were involved with acquisition of data, critical revision of the manuscript for important intellectual content and approval of the final version of the manuscript. ICKW and WKL were involved in the critical revision of the manuscript for important intellectual content and study supervision.

  • Competing interests WKL has received honorarium for attending advisory board meetings of Takeda and Abbott Laboratories.

  • Ethics approval Institutional Review Board of the University of Hong Kong and the West Cluster of Hospital Authority, Hong Kong.

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

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