Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori : a population-based study
Open accessAbstract
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.
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Some studies and meta-analyses report an increased risk of developing GC in long-term PPI users up to 2.4 times greater, even after H. pylori eradication.
“with some studies and meta-analyses reporting an increased risk of developing GC in long-term PPI users[62,63] up to 2.4 times greater, even after Helicobacter pylori (H. pylori) eradication, according to a recent study[64]”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [64]
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- Authors
- Cheung, K. S., Chan, E. W., Wong, A. Y. S., Chen, L., Wong, I. C. K., & Leung, W. K.
- Affiliations
- Queen Mary Hospital (CN)
- University of Hong Kong (HK)
- UCL School of Pharmacy (GB)
- Corresponding author
- Leung, Wai Keung
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-10-31
- Volume
- 67
- Issue
- 1
- Pages
- 28-35
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2766436834
- Cited by
- 455
- References
- 33
- Citations by year
- 2026: 38 · 2025: 27 · 2024: 45 · 2023: 45 · 2022: 48 · 2021: 65 · 2020: 53 · 2019: 65 · 2018: 59 · 2017: 10
- FWCI
- 52.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- proton pump inhibitors, gastric cancer, Helicobacter pylori infection, H. pylori eradication therapy, clarithromycin-based triple therapy, H2 receptor antagonists, long-term PPI use, gastric cancer risk
- MeSH terms
- Aged, Anti-Bacterial Agents, Drug Administration Schedule, Drug Therapy, Combination, Female, Hong Kong, Humans, Male, Middle Aged, Stomach Neoplasms, Incidence, Databases, Factual, Helicobacter pylori, Helicobacter Infections, Clarithromycin, Risk Assessment, Proton Pump Inhibitors
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