Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis.
OBJECTIVE
Acid-suppressive medications, particularly proton pump inhibitors (PPIs), may decrease the risk of oesophageal adenocarcinoma (OAC) in patients with Barrett's oesophagus (BO). We performed a systematic review with meta-analysis of studies evaluating the association between acid-suppressive medications (PPIs and histamine receptor antagonists (H2RAs)) and risk of OAC or high-grade dysplasia (BO-HGD) in patients with BO.


METHODS
We performed a systematic search of multiple electronic databases and conference proceedings up to June 2013 to identify studies reporting the association between use of acid-suppressive medications and risk of OAC and/or BO-HGD in patients with BO. Summary ORs with 95% CIs were estimated.


RESULTS
We identified seven observational studies (2813 patients with BO, 317 cases of OAC or BO-HGD, 84.4% PPI users). On meta-analysis, PPI use was associated with a 71% reduction in risk of OAC and/or BO-HGD in patients with BO (adjusted OR 0.29; 95% CI 0.12 to 0.79). There was a trend towards a dose-response relationship with PPI use for >2-3 years protective against OAC or BO-HGD (three studies; PPI use >2-3 years vs <2-3 years: OR 0.45 (95% CI 0.19 to 1.06) vs 1.09 (0.47 to 2.56)). Considerable heterogeneity was observed. Two studies reported the association between H2RA use and risk of OAC and/or BO-HGD (1352 patients with BO, 156 cases of OAC, 25.4% on H2RAs), and both studies did not show a significant effect.


CONCLUSIONS
Based on meta-analysis of observational studies, the use of PPIs is associated with a decreased risk of OAC and/or BO-HGD in patients with BO. None of the studies showed an increased risk of OAC. PPI use should be considered in BO, and chemopreventive trials of PPIs in patients with BO are warranted.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Siddharth
S
Singh
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
Sushil Kumar
SK
Garg
Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Preet Paul
PP
Singh
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Prasad G
PG
Iyer
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA.
Hashem B
HB
El-Serag
D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D001471:Barrett Esophagus / Q000188:drug therapy*; D004938:Esophageal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D064887:Observational Studies as Topic; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D018570:Risk Assessment
D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors
Anti-Reflux Therapy; Barrett's Oesophagus; Cancer Prevention