By Lisa Rapaport
May 21, 2021
(Reuters Health) – Taking proton pump inhibitors (PPIs) is associated with increased risk of developing gastric cancer regardless of Helicobacter pylori eradication status, a Korean study suggests.
Researchers examined data in the Korean National Health Insurance Service database on 6,877 patients who initiated PPI therapy and 6,877 propensity matched controls who didn’t use PPIs. Over a median follow-up of 4.4 years in the PPI group, 118 patients developed gastric cancer, compared with 40 cases of gastric cancer in the non-PPI group followed for a median 4.2 years.
Compared with non-PPI users, patients who used PPIs for 30 days or more were significantly more likely to develop gastric cancer (hazard ratio 2.37).
In addition, researchers found the subset of patients with eradicated chronic H. pylori infection were significantly more likely to develop gastric cancer if they used PPIs for 180 days or more than if they didn’t use the medications (HR 2.22).
“The findings from this study tell us that the increased risk is unlikely to be related to H. pylori and further raises the specter that this risk may be attributable to the drug itself,” said Dr. Ziyad Al-Aly, chief of the research and development service at the VA Saint Louis Health Care System in Missouri.
“It is increasingly clear that PPIs are associated with a host of adverse events including gastric cancer,” Dr. Al-Aly, who wasn’t involved in the study, said by email. “The evidence keeps mounting from different studies done by different groups in different countries using a range of methods including causal inference methods.”
Patients were matched for usage of medications thought to influence the risk of gastric cancer including aspirin, metformin, NSAIDs, antirheumatic drugs, and statins.
H. pylori eradication therapy was provided for 2.9% of PPI users and 2.5% of non-PPI users in the study.
One limitation of the study is that researchers lacked data on H. pylori infection status and on results from rapid urease or urea breath tests to confirm eradication status, the authors note in Gut. Senior author Dr. Woon Geon Shin of Kangdong Sacred Heart Hospital and Hallym University College of Medicine in Seoul, South Korea, didn’t respond to requests for comment.
It’s also possible that the PPI cohort had patients with more severe cases of H. Pylori and ulcers than the non-PPI group because PPIs have superior gastric pH control over alternative therapies, said Ruben Abagyan, a professor of pharmacy at the University of California, San Diego, who wasn’t involved in the study.
“Thus, higher occurrences of gastric cancer might have been the consequence of the underlying condition that is correlated with the treatment rather than the treatment,” Abagyan said by email.
Even so, clinicians should be aware that H. pylori eradication by itself isn’t sufficient to entirely prevent gastric cancer, Abagyan said.
“The gastrointestinal ulcers as open sores result in continuous and often chronic inflammation, which increases the risk of gastrointestinal cancers,” Abagyan said. “This risk may be increased by the infection; however, the infection is not the main culprit.”
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