medwireNews: The long-term use of proton pump inhibitors (PPIs) for gastric acid-related disorders is associated with an elevated risk for gastric cancer in individuals who have received treatment for Helicobacter pylori infection, a population-based study indicates.
The researchers explain that PPI use for over a year has previously been linked with an increased gastric cancer risk, but “these results are largely confounded by the unknown prevalence of H. pylori in the study population,” which is why they focused on patients who had been prescribed at least a 7-day course of clarithromycin-based triple therapy for H. pylori eradication.
The chart review included data drawn from the Clinical Data Analysis and Reporting System of the Hong Kong Hospital Authority on 63,397 patients treated for H. pylori between 2003 and 2012, of whom 153 (0.24%) developed gastric cancer over a median follow-up of 7.6 years. This equated to an overall incidence of gastric cancer in this cohort of 3.2 cases per 10,000 person–years.
Individuals who used PPIs (n=3271) at least once a week after receiving clarithromycin-based therapy were significantly more likely to develop gastric cancer than their counterparts who did not use PPIs (n=60,126; defined as less than weekly use), with a hazard ratio (HR) of 2.44 after propensity score adjustment with trimming.
By contrast, use of histamine-2 receptor antagonists was not associated with an elevated gastric cancer risk (nonsignificant HR=0.72), which “further supports the specific role of PPIs on gastric cancer development,” Wai Keung Leung (Queen Mary Hospital, Hong Kong) and co-authors write in Gut.
They also identified a dose- and time-dependent effect of PPI use, with the highest risks seen among daily users (HR=4.55) and those who took PPIs once a day for at least 3 years (HR=8.34) relative to nonusers.
However, the overall absolute risk difference between PPI users and nonusers was 4.29 excess gastric cancer cases per 10,000 person–years.
Speaking to the press, independent commentator Stephen Evans, from the London School of Hygiene & Tropical Medicine in the UK, emphasized that “[t]he absolute risk is small.”
He added: “If a patient notices improvement in the quality of their life in taking a PPI, they may be prepared to trade the fairly small excess risk of gastric cancer for that improvement.
“However, on a precautionary principle, if the PPI is not necessary, it should not be taken for longer than is required.”
Evans also pointed out that as the study is observational in design, no conclusion can be drawn regarding causality, and “[i]n order to be certain of a causal effect we would need extremely large randomised trials.”
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