Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden
Open accessAbstract
Objective: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to assess the risk of gastric cancer associated with PPI use, taking into account underlying indications. Design: This is a population-based cohort study. Standardised incidence ratios (SIRs) and 95% CIs were calculated to compare the risk of gastric cancer among long-term PPI users with the corresponding background population, while taking confounding by indication into account. Setting: Population-based study in Sweden (2005–2012). Participants: This study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs. Exposure/Intervention: Maintenance use of PPIs, defined as at least 180 days during the study period. Maintenance use of histamine 2 receptor antagonist was evaluated for comparison reasons. Outcome measures: Gastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry. Results: Among 797 067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95% CI 3.23 to 3.53). Increased SIRs were found in both sexes and all age groups, but were especially increased among PPI users younger than 40 years (SIR=22.76, 95% CI 15.94 to 31.52). Increased SIRs were found for each indication studied, including those without an association with gastric cancer, for example, gastro-oesophageal reflux (SIR=3.04, 95% CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95% CI 1.70 to 2.18). The association was similar for cardia and non-cardia gastric cancer. Analyses restricted to adenocarcinoma showed similar results to those for all gastric cancers. Long-term users of histamine 2 receptor antagonists, which have the same indications as PPIs, were not at any increased risk. Conclusions: Long-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak.
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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 [63]
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- Authors
- Brusselaers, N., Wahlin, K., Engstrand, L., & Lagergren, J.
- Affiliations
- Science for Life Laboratory (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Brusselaers, Nele
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2017-10
- Volume
- 7
- Issue
- 10
- Pages
- e017739
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC5665226
- OpenAlex
- W2767066701
- Cited by
- 204
- References
- 34
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 20 · 2023: 24 · 2022: 24 · 2021: 34 · 2020: 26 · 2019: 32 · 2018: 22 · 2017: 3
- FWCI
- 23.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Cancerfonden
- SFO Epidemiology
- Karolinska Institutet
- Vetenskapsrådet
- 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, gastric adenocarcinoma, long-term drug use, maintenance therapy, confounding by indication, H2 receptor antagonists, gastroesophageal reflux, aspirin, gastric cancer risk factors, young adults, gastric cardia cancer, Sweden, drug safety, prescribing patterns, Helicobacter pylori
- MeSH terms
- Adenocarcinoma, Adult, Age Factors, Aged, Aged, 80 and over, Aspirin, Female, Gastroesophageal Reflux, Histamine H2 Antagonists, Humans, Male, Middle Aged, Risk Factors, Stomach Neoplasms, Sweden, Time Factors, Cohort Studies, Incidence, Proton Pump Inhibitors
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