Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study

• Published in: Gut Vol. 67; no. 1; pp. 28 - 35
• Main Authors: Cheung, Ka Shing, Chan, Esther W, Wong, Angel Y S, Chen, Lijia, Wong, Ian C K, Leung, Wai Keung
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.01.2018; BMJ Publishing Group LTD
• Subjects: Acids; Aged; Anti-Bacterial Agents - therapeutic use; Atrophy; Bias; Clarithromycin; Clarithromycin - therapeutic use; Clinical medicine; Databases, Factual; Drug Administration Schedule; Drug Therapy, Combination; Female; gastric adenocarcinoma; Gastric cancer; Health risk assessment; Helicobacter Infections - complications; Helicobacter Infections - drug therapy; Helicobacter Infections - epidemiology; Helicobacter pylori; Histamine; Hong Kong - epidemiology; Humans; Incidence; Infections; Male; Middle Aged; Patients; Population; Population studies; Population-based studies; Prescriptions; Proton pump inhibitors; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - adverse effects; Risk Assessment; Stomach; stomach cancer; Stomach Neoplasms - chemically induced; Stomach Neoplasms - epidemiology; Stomach Neoplasms - microbiology; Studies; Substance abuse treatment; Territory; Ulcers; Hong Kong China; China; Helicobacterpylori; stomach cancer; gastric adenocarcinoma
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2017-314605

ObjectiveProton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy.DesignsThis study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure.ResultAmong the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years.ConclusionLong-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.