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Long-term proton pump inhibitor use associated with increased risk of gastric cancer

Dr. Joseph Delano Fule Robles
14 Nov 2017
From left: Dr Esther Wai-Yin Chan, Prof Wai-Keung Leung, Dr Michael Ka-Shing Cheung

A recent study conducted by The University of Hong Kong (HKU) revealed that long-term use of proton pump inhibitors (PPIs) is associated with a significantly increased risk of gastric cancer even in patients who have had Helicobacter pylori eradicated.

In the territory-wide population-based study composed of 63,397 eligible patients treated with clarithromycin-based triple therapy, weekly PPI use was associated with a more than two-fold increased risk for gastric cancer (hazard ratio [HR], 2.43; p=0.002). [Gut 2017, doi: 10.1136/gutjnl-2017-314605]

The adjusted absolute risk difference for PPI use vs non-PPI use was 4.29 excess gastric cancers per 10,000 person-years.

Daily PPI use increased the risk of gastric cancer by more than four-fold (HR, 4.55; p=0.034), with incremental increases in risk found with the duration of PPI use (HR for ≥1 year: 5.04, p=0.024; HR for ≥ 2 years: 6.65, p=0.009; HR for ≥ 3 years: 8.34, p=0.004)

“We found that the long-term use of PPIs doubled the risk of gastric cancer development even after successful H. pylori eradication.  The risk rose in tandem with the dose and duration of PPI treatment,” said investigator Professor Wai-Keung Leung of the Department of Medicine, Li Ka Shing Faculty of Medicine, HKU.

This increase in risk was not observed among patients who used histamine-2 receptor antagonists [HR from propensity score adjustment, 0.72].

“Gastric atrophy is considered to be a precursor for gastric cancer. While PPIs are potent acid suppressors, there is a possibility that they can worsen gastric atrophy,” the authors said.

Further analysis showed that the incidence rate (IR) of gastric cancer was higher among patients given PPIs with prior H. pylori eradication therapy vs those given PPIs without prior H. pylori eradication therapy (crude IR per 10,000 person-years, 8.1 vs 0.8).

All the gastric cancers were verified to be adenocarcinoma, with 20.3 percent located in the cardia and 62.1 percent in the non-cardia regions.

PPI use was, however, found to be significantly associated with an increased risk of non-cardia gastric cancer, but not cardia gastric cancer (HR, 2.59 vs 1.97).

In the study, PPI users were older than non-PPI users by around 10 years, and the HR of gastric cancer with increasing age was 1.06 on multivariable analysis.

“However, as this is an observational study, no firm conclusions can be drawn about causality, and PPIs are generally considered safe. The use of PPIs should not be discouraged, but regular review of the indications of the prescribed PPIs is recommended, and PPIs should be used at the minimum effective dose, frequency and duration,” the authors commented.

The authors also recommended that even after successful eradication of H. pylori, physicians should exercise caution when prescribing PPIs on a long-term basis.

A meta-analysis previously showed that the risk of gastric cancer is increased by 43 percent among PPI users regardless of their H. pylori status. [Clin Gastroenterol Hepatol 2016;14:1706-1719]

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