{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:45:45Z","timestamp":1793835945120,"version":"4.6.1"},"reference-count":51,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therap Adv Gastroenterol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec><jats:title>Introduction:<\/jats:title><jats:p> The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC). <\/jats:p><\/jats:sec><jats:sec><jats:title>Objective:<\/jats:title><jats:p> To review and meta-analyse available literature investigating the association between PPI use and GC risk. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> 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 (&lt;1 year, 1\u20133 years, &gt;3 years). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> 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\u20132.56] with high statistical heterogeneity ( I<jats:sup>2<\/jats:sup>\u2009=\u200982%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44\u20133.36, I<jats:sup>2<\/jats:sup>\u2009=\u200977%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72\u20134.36, I<jats:sup>2<\/jats:sup>\u2009=\u200966%). There was no GC increase with longer durations of PPI exposure (&lt;1 year: OR: 2.29, 95% CI: 2.13\u20132.47, I<jats:sup>2<\/jats:sup>\u2009=\u20090%; 1\u20133 years: OR: 1.46, 95% CI: 0.53\u20134.01, I<jats:sup>2<\/jats:sup>\u2009=\u200935%; &gt;3 years: OR: 2.08, 95% CI: 0.56\u20137.77, I<jats:sup>2<\/jats:sup>\u2009=\u200961%). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec>","DOI":"10.1177\/17562848211051463","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T12:25:32Z","timestamp":1636547132000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":46,"title":["Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1598-8595","authenticated-orcid":false,"given":"Daniel","family":"Segna","sequence":"first","affiliation":[{"name":"Hepatology, Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Freiburgstrasse 4, 8010 Bern, Switzerland"},{"name":"Clinic of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland"},{"name":"Clinic of Gastroenterology, Department of Internal Medicine, GZO Wetzikon, Wetzikon, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-447X","authenticated-orcid":false,"given":"Nele","family":"Brusselaers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Glaus","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Krupka","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Misselwitz","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland"},{"name":"Clinic of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"bibr1-17562848211051463","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"bibr2-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11426"},{"key":"bibr3-17562848211051463","volume":"150","author":"Lee YC","year":"2016","journal-title":"Gastroenterology"},{"key":"bibr4-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2009.04.019"},{"key":"bibr5-17562848211051463","volume":"351","author":"Song H","year":"2015","journal-title":"BMJ"},{"key":"bibr6-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-13-1057"},{"key":"bibr7-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39406.449456.BE"},{"key":"bibr8-17562848211051463","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i16.2560"},{"key":"bibr9-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2016.05.018"},{"key":"bibr10-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14759"},{"key":"bibr11-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316416"},{"key":"bibr12-17562848211051463","doi-asserted-by":"publisher","DOI":"10.36159\/jgs.v2i1.17"},{"key":"bibr13-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-020-02927-8"},{"key":"bibr14-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2019.101585"},{"key":"bibr15-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316371"},{"key":"bibr16-17562848211051463","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000591"},{"key":"bibr17-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0860-4"},{"key":"bibr18-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"key":"bibr19-17562848211051463","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.84"},{"key":"bibr20-17562848211051463","volume":"355","author":"Sterne JA","year":"2016","journal-title":"BMJ"},{"key":"bibr21-17562848211051463","unstructured":"Sterne JACHM, McAleenan A, Reeves BC, et al. 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