Long-term use of proton pump inhibitors (PPIs) may not increase the risk of developing stomach cancer, according to a large multinational study published recently in The BMJ.
PPIs are widely prescribed for conditions such as gastro-oesophageal reflux disease (GORD) and peptic ulcers, but concerns about a possible link to gastric cancer have reportedly persisted since the 1980s.
While some studies suggest a 2-fold increased risk, researchers say those findings were limited by significant methodological weaknesses.
The study
To address these concerns, researchers analysed high-quality healthcare registry data from Denmark, Finland, Iceland, Norway and Sweden over a 26-year period (1994–2020).
The study identified 17,232 patients with stomach cancer and randomly matched each case with 10 controls by age, sex, country and calendar year — a total of 172,297 people.
Researchers examined long-term (more than 1 year) PPI use and histamine-2-receptor antagonists (H2-blockers), excluding the 12 months before the diagnosis date or study inclusion to avoid false associations linked to early symptoms of undiagnosed cancer.
The analysis adjusted for multiple confounding factors, including age, sex, Helicobacter pylori eradication therapy, smoking- and alcohol-related disease, obesity, type 2 diabetes, peptic ulcer disease and use of other medications.
After adjusting for these factors, the researchers found no remaining association between long-term use of PPIs or H2-blockers and increased risk of stomach cancer.
Limitations of an observational study
While the authors note the study’s observational design means no firm conclusions can be drawn about cause and effect — and that factors such as diet and family history weren’t captured — they emphasise the strength of the dataset and the methodological rigour used to address known biases.
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.”
The findings of this study should offer relief for patients needing long-term PPI therapy and are valuable for clinical decision-making in healthcare settings, say the researchers.
