Proton pump inhibitors are among the most commonly prescribed medications worldwide, but concerns about a possible link to stomach cancer have lingered for decades.
Proton pump inhibitors (PPIs) are among the most frequently prescribed medications for managing chronic acid reflux and peptic ulcer disease. Despite their widespread use, questions have lingered for decades about whether taking these drugs over long periods could raise the risk of gastric (stomach) cancer. A large new study drawing on health data from Nordic countries now suggests that such concerns may be unfounded.
Published by The BMJ, the research indicates that long-term PPI therapy was not associated with a higher likelihood of developing stomach cancer. According to the authors, the findings may ease anxiety for patients who depend on these medications and support more confident decision-making in clinical care.
The idea that proton pump inhibitors might contribute to stomach cancer dates back to the 1980s, when scientists first began examining the long-term biological effects of suppressing stomach acid. In more recent years, some studies have reported links between PPI use and roughly double the risk of gastric cancer. However, many of those studies struggled to separate cause from coincidence, often failing to fully account for underlying conditions that themselves increase cancer risk.
A Study Designed to Address Past Limitations
To address these uncertainties, researchers designed a study that explicitly targeted the weaknesses seen in earlier research. Rather than focusing on smaller patient groups, they turned to national healthcare registries that capture decades of medical information across entire populations.
The study analyzed data from Denmark, Finland, Iceland, Norway, and Sweden, covering a 26-year period from 1994 to 2020. Within these records, the researchers identified 17,232 people diagnosed with stomach cancer (cases) and matched each one with 10 individuals without the disease (controls) from the general population. Matching was based on age, sex, calendar year, and country, producing a comparison group of 172,297 participants.
The team examined long-term use, defined as more than one year, of proton pump inhibitors as well as histamine-2-receptor antagonists (another class of drugs used to reduce stomach acid). To minimize the risk that early symptoms of cancer influenced medication use, the researchers excluded drug exposure during the 12 months before the cancer diagnosis date (cases) or study entry date (controls).
Because stomach cancer is influenced by many biological and lifestyle factors, the analysis also accounted for key contributors to risk. These included age and sex, treatment for Helicobacter pylori infection (the bacteria implicated in the development of stomach cancer), a history of peptic ulcer disease, smoking and alcohol related diseases, obesity or type 2 diabetes, and the use of certain medications.
After adjusting for all of these variables, the researchers found no evidence that long term use of proton pump inhibitors or histamine-2-receptor antagonists was associated with an increased risk of stomach cancer.
Interpreting the Results
This is an observational study, so no firm conclusions can be drawn about cause and effect. And despite extensive efforts, the authors can’t rule out the possibility that unmeasured factors, such as diet and family history of stomach cancer, may have affected the results.
However, they note that this multinational study based on up to 26 years of high-quality registry data allowed them to mitigate many of the biases and other problems affecting previous research on this topic.
As such, they conclude: “The results of this study do not support the hypothesis that long-term proton pump inhibitor use is associated with an increased risk of gastric adenocarcinoma.”
“This finding should offer relief for patients needing long-term proton pump inhibitor therapy and is valuable for healthcare in clinical decision making,” they add.
Reference: “Long term use of proton pump inhibitors and risk of stomach cancer: population based case-control study in five Nordic countries” by Onyinyechi Duru, Giola Santoni, Dag Holmberg, Helgi Birgisson, Joonas H Kauppila, My von Euler-Chelpin, Eivind Ness-Jensen and Jesper Lagergren, 21 January 2026, BMJ.
DOI: 10.1136/bmj-2025-086384
Funding: Swedish Research Council, Nordic Cancer Union, Swedish Cancer Society
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1 Comment
Good news