PPIs are among the most commonly prescribed drugs worldwide, helping reduce stomach acid and manage conditions like gastroesophageal reflux disease (GERD) and peptic ulcers. While their benefits are clear, concerns about a possible link to stomach cancer have persisted since the 1980s.
Some previous studies suggested a twofold increase in risk, but methodological limitations made it difficult to draw solid conclusions. This latest research aimed to clarify the issue using robust data and rigorous methods.
Researchers collected healthcare registry information from Denmark, Finland, Iceland, Norway, and Sweden spanning 26 years, from 1994 to 2020. They identified 17,232 patients diagnosed with stomach cancer and matched each with 10 healthy controls—totaling 172,297 individuals—accounting for age, sex, calendar year, and country. Long-term use of PPIs and histamine-2-receptor antagonists (another class of acid-reducing drugs) was recorded, excluding the 12 months prior to diagnosis to avoid falsely linking short-term use with cancer.
The team also considered other factors that might influence risk, including previous Helicobacter pylori infection, peptic ulcers, smoking, alcohol-related illnesses, obesity, type 2 diabetes, and the use of other medications. After adjusting for these variables, the analysis found no evidence that long-term PPI or histamine-2-receptor antagonist use increases the likelihood of developing gastric cancer.
These findings offer reassurance for patients who rely on long-term acid-reducing therapy. They highlight that PPIs remain a safe option for managing chronic acid-related conditions and provide valuable guidance for clinicians making decisions about long-term treatment strategies.
REFERENCE: Onyinyechi Duru, Giola Santoni, Dag Holmberg, Helgi Birgisson, Joonas H Kauppila, My von Euler-Chelpin, Eivind Ness-Jensen, Jesper Lagergren; Long term use of proton pump inhibitors and risk of stomach cancer: population based case-control study in five Nordic countries; BMJ 2026; doi: https://doi.org/10.1136/bmj-2025-086384
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