Proton pump inhibitors and risk of gastric cancer: a population-based cohort study

ObjectiveTo determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs).DesignUsing the UK Clinical Practice Research Datalink, we conducted a population-based cohort study using a new-user active comparator design. From 1 January 1990 to 30 April 2018, we identified 973 281 new users of PPIs and 193 306 new users of H2RAs. Cox proportional hazards models were fit to estimate HRs and 95% CIs of gastric cancer, and the number needed to harm was estimated using the Kaplan-Meier method. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Secondary analyses assessed duration and dose–response associations.ResultsAfter a median follow-up of 5.0 years, the use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2RAs (HR 1.45, 95% CI 1.06 to 1.98). The number needed to harm was 2121 and 1191 for five and 10 years after treatment initiation, respectively. The HRs increased with cumulative duration, cumulative omeprazole equivalents and time since treatment initiation. The results were consistent across several sensitivity analyses.ConclusionThe findings of this large population-based cohort study indicate that the use of PPIs is associated with an increased risk of gastric cancer compared with the use of H2RAs, although the absolute risk remains low.

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Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden

BMJ Open ◽

10.1136/bmjopen-2017-017739 ◽

2017 ◽

Vol 7 (10) ◽

pp. e017739 ◽

Cited By ~ 69

Author(s):

Nele Brusselaers ◽

Karl Wahlin ◽

Lars Engstrand ◽

Jesper Lagergren

Keyword(s):

Gastric Cancer ◽

Cohort Study ◽

Maintenance Therapy ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Age Groups ◽

Population Based ◽

Background Population ◽

Increased Risk

ObjectiveProton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to assess the risk of gastric cancer associated with PPI use, taking into account underlying indications.DesignThis is a population-based cohort study. Standardised incidence ratios (SIRs) and 95% CIs were calculated to compare the risk of gastric cancer among long-term PPI users with the corresponding background population, while taking confounding by indication into account.SettingPopulation-based study in Sweden (2005–2012).ParticipantsThis study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs.Exposure/InterventionMaintenance use of PPIs, defined as at least 180 days during the study period. Maintenance use of histamine 2 receptor antagonist was evaluated for comparison reasons.Outcome measuresGastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry.ResultsAmong 797 067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95% CI 3.23 to 3.53). Increased SIRs were found in both sexes and all age groups, but were especially increased among PPI users younger than 40 years (SIR=22.76, 95% CI 15.94 to 31.52). Increased SIRs were found for each indication studied, including those without an association with gastric cancer, for example, gastro-oesophageal reflux (SIR=3.04, 95% CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95% CI 1.70 to 2.18). The association was similar for cardia and non-cardia gastric cancer. Analyses restricted to adenocarcinoma showed similar results to those for all gastric cancers. Long-term users of histamine 2 receptor antagonists, which have the same indications as PPIs, were not at any increased risk.ConclusionsLong-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak.

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