Long-term use of proton pump inhibitors (PPIs) more than doubles the risk of gastric cancers, according to research published this week in Gut.
The Hong Kong-based study included over 63,000 people who had undergone successful eradication of Helicobacter pylori infections. H. pylori infections are linked to stomach cancer and their eradication reduces risk. But a significant number of those who have had the infection eradicated will still go on to develop stomach cancer.
In this cohort, 153 study participants went on to develop gastric cancer, with a median follow-up of 7.5 years. Those who did develop cancer were 2.4 times more likely to have been long-term users of PPIs. The cancer risk rose with higher dosages and longer-term use of PPIs: those who used PPIs daily more than quadrupled their risk of gastric cancer, while more than a year of regular use resulted in a fivefold increase in risk.
However, users of histamine H2 receptor antagonists (H2RAs), another common acid reflux therapy, did not see their risk of gastric cancer rise.
The study authors say that the association is likely to be related to the profound acid suppression of PPIs that worsens atrophic gastritis, a known risk factor in gastric cancer. They say the lack of an association with H2RAs and gastric cancer further supports a specific role for PPIs in gastric cancer development.
“Physicians should therefore exercise caution when prescribing long-term PPIs to these patients even after successful eradication of H. pylori,” the authors conclude.
Commenting on the study, Associate Professor Richard Ferrero, who heads up a GI infection and inflammation research group at the Hudson Institute of Medical Research in Melbourne, said a study published in 1996 first raised alarm over possible deleterious effects of PPIs, showing that people with a H. pylori infection increased their risk of cancer if they were on PPI therapy. Since then, H. pylori eradication has been recommended before long-term PPI treatment.
“This new study now shows that even a prior H. pylori infection increases the risk of gastric cancer in subjects receiving long-term PPI therapy,” Dr Ferrero said. “The work has important implications as PPIs, which are among the top 10 selling generic drugs, are commonly prescribed to treat heartburn.”
He said the study’s design eliminated a number of important confounding factors, although the authors were unable to obtain detailed histological findings on gastric biopsies from participants.
“This may have helped explain why stomachs that have previously been infected with H. pylori are more likely to develop cancer in response to long-term PPI treatment,” Dr Ferrero commented.
Recent studies have linked PPIs to a string of unwanted effects, including pneumonia, dementia, cardiovascular problems and bone fracture.
You can access the study here.