Maintenance proton pump inhibition therapy and risk of oesophageal cancer
Abstract
Background The association of long-term use of proton pump inhibitors (PPIs) with oesophageal adenocarcinoma has been poorly defined. Our aim was to assess the risk of oesophageal cancer assessing confounding by indication.Methods This population-based cohort study included all 796,492 adults exposed to maintenance therapy with PPIs in Sweden in 2005-2012. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to assess the risk of oesophageal adenocarcinoma (and squamous cell carcinoma as a comparison) among long-term PPI users relative to the corresponding background population. The different indications for maintenance PPI therapy were analysed separately.Results Among all individuals using maintenance PPI therapy, the overall SIR of oesophageal adenocarcinoma was 3.93 (95% CI 3.63-4.24). The SIRs of adenocarcinoma were increased also among individuals without gastro-oesophageal reflux disease who used PPIs for indications not associated with any increased risk of oesophageal adenocarcinoma. For example, the SIRs among participants using maintenance PPI therapy because of maintenance treatment with non-steroidal anti-inflammatory drugs and aspirin were 2.74 (95% CI 1.96-3.71) and 2.06 (95% CI 1.60-2.60), respectively. The SIRs of oesophageal squamous cell carcinoma were increased for most investigated indications, but to a lesser degree than for oesophageal adenocarcinoma.Conclusion In conclusion, the long term use of PPIs is associated with increased risk of oesophageal adenocarcinoma in the absence of other risk factors. Long term use of PPIs should be addressed with caution.
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Long-term use of PPIs is associated with an increased risk of EAC in the absence of other risk factors.
“A recent epidemiological study revealed that, in the absence of other risk factors, the long-term use of PPIs is associated with an increased risk of EAC[48].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [48]
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Transoral Fundoplication for Treatment of Gastroesophageal Reflux Disease
Testoni, S. G. G., Fanti, L., & Testoni, P. A. (2021) · Springer eBooks · doi:10.1007/978-3-030-56993-8_38
Transoral Fundoplication for Treatment of Gastroesophageal Reflux Disease
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Esophageal Adenocarcinoma: Pathogenesis and Epidemiology
Lezama, M. M., Schlottmann, F., & Patti, M. G. (2023) · Springer eBooks · doi:10.1007/978-3-031-39086-9_3
Efeitos do uso prolongado de Inibidores de Bomba de Prótons e neoplasias
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Protonpumpehemmarar mot spiserørskreft – til nytte eller skade?
Raknes, G. (2024) · Tidsskrift for Den norske legeforening · doi:10.4045/tidsskr.24.0480
Helicobacter pylori in esophageal carcinogenesis: Potential culprit or forceful defender?
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Sayyid, R. K., Tiwari, R. V., Zhang, B., Wilton, A. S., Lajkosz, K., Cockburn, J., Bernardino, R. M. M., Al‐Daqqaq, Z., Penn, L. Z., Goldberg, H., et al. (2026) · Cancer Research Communications · doi:10.1158/2767-9764.crc-26-0098
- Authors
- Brusselaers, N., Engstrand, L., & Lagergren, J.
- Affiliations
- Karolinska University Hospital (SE)
- Science for Life Laboratory (SE)
- Corresponding author
- Brusselaers, Nele
- Venue
- Cancer Epidemiology
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 53
- Pages
- 172-177
- ISSN
- 1877-7821 (ISSN-L)
- OpenAlex
- W2793897631
- Cited by
- 80
- References
- 37
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 12 · 2022: 7 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 11
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Health Sciences › Medicine › Surgery › Esophageal and GI Pathology
- Keywords
- proton pump inhibitors, esophageal adenocarcinoma, esophageal squamous cell carcinoma, long-term drug use, confounding by indication, gastroesophageal reflux disease, nonsteroidal anti-inflammatory drugs, aspirin, cancer risk
- MeSH terms
- Adenocarcinoma, Adult, Aged, Carcinoma, Squamous Cell, Esophageal Neoplasms, Female, Humans, Male, Middle Aged, Risk Factors, Sweden, Cohort Studies, Proton Pump Inhibitors
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