Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

Introduction: The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC). Objective: To review and meta-analyse available literature investigating the association between PPI use and GC risk. Methods: Two independent reviewers systematically searched Ovid...

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Autores principales:	Daniel Segna, Nele Brusselaers, Damian Glaus, Niklas Krupka, Benjamin Misselwitz
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/924dd09202ec453aaa541906d990a963
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spelling	oai:doaj.org-article:924dd09202ec453aaa541906d990a9632021-11-10T23:03:47ZAssociation between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis1756-284810.1177/17562848211051463https://doaj.org/article/924dd09202ec453aaa541906d990a9632021-10-01T00:00:00Zhttps://doi.org/10.1177/17562848211051463https://doaj.org/toc/1756-2848Introduction: The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC). Objective: To review and meta-analyse available literature investigating the association between PPI use and GC risk. Methods: Two independent reviewers systematically searched Ovid MEDLINE, EMBASE, and Cochrane Library (inception to July 2020) for case-control and cohort studies assessing the association between PPI use and GC according to a predefined protocol in PROSPERO (CRD42018102536). Reviewers independently assessed study quality, extracted data, and meta-analysed available and newly calculated odds ratios (ORs) using a random-effects model, and stratified for GC site (cardia versus non-cardia) and PPI duration (<1 year, 1–3 years, >3 years). Results: We screened 2,396 records and included five retrospective cohort and eight case-control studies comprising 1,662,881 individuals in our meta-analysis. In random-effect models, we found an increased GC risk in PPI users [OR: 1.94, 95% confidence interval (95% CI): 1.47–2.56] with high statistical heterogeneity ( I 2 = 82%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44–3.36, I 2 = 77%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72–4.36, I 2 = 66%). There was no GC increase with longer durations of PPI exposure (<1 year: OR: 2.29, 95% CI: 2.13–2.47, I 2 = 0%; 1–3 years: OR: 1.46, 95% CI: 0.53–4.01, I 2 = 35%; >3 years: OR: 2.08, 95% CI: 0.56–7.77, I 2 = 61%). Conclusion: We found a twofold increased GC risk among PPI users, but this association does not confirm causation and studies are highly heterogeneous. PPI should only be prescribed when strictly indicated.Daniel SegnaNele BrusselaersDamian GlausNiklas KrupkaBenjamin MisselwitzSAGE PublishingarticleDiseases of the digestive system. GastroenterologyRC799-869ENTherapeutic Advances in Gastroenterology, Vol 14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Diseases of the digestive system. Gastroenterology RC799-869 Daniel Segna Nele Brusselaers Damian Glaus Niklas Krupka Benjamin Misselwitz Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
description	Introduction: The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC). Objective: To review and meta-analyse available literature investigating the association between PPI use and GC risk. Methods: Two independent reviewers systematically searched Ovid MEDLINE, EMBASE, and Cochrane Library (inception to July 2020) for case-control and cohort studies assessing the association between PPI use and GC according to a predefined protocol in PROSPERO (CRD42018102536). Reviewers independently assessed study quality, extracted data, and meta-analysed available and newly calculated odds ratios (ORs) using a random-effects model, and stratified for GC site (cardia versus non-cardia) and PPI duration (<1 year, 1–3 years, >3 years). Results: We screened 2,396 records and included five retrospective cohort and eight case-control studies comprising 1,662,881 individuals in our meta-analysis. In random-effect models, we found an increased GC risk in PPI users [OR: 1.94, 95% confidence interval (95% CI): 1.47–2.56] with high statistical heterogeneity ( I 2 = 82%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44–3.36, I 2 = 77%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72–4.36, I 2 = 66%). There was no GC increase with longer durations of PPI exposure (<1 year: OR: 2.29, 95% CI: 2.13–2.47, I 2 = 0%; 1–3 years: OR: 1.46, 95% CI: 0.53–4.01, I 2 = 35%; >3 years: OR: 2.08, 95% CI: 0.56–7.77, I 2 = 61%). Conclusion: We found a twofold increased GC risk among PPI users, but this association does not confirm causation and studies are highly heterogeneous. PPI should only be prescribed when strictly indicated.
format	article
author	Daniel Segna Nele Brusselaers Damian Glaus Niklas Krupka Benjamin Misselwitz
author_facet	Daniel Segna Nele Brusselaers Damian Glaus Niklas Krupka Benjamin Misselwitz
author_sort	Daniel Segna
title	Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
title_short	Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
title_full	Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
title_fullStr	Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
title_full_unstemmed	Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
title_sort	association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/924dd09202ec453aaa541906d990a963
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Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

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