{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:39:31Z","timestamp":1791272371817,"version":"4.1.0"},"reference-count":33,"publisher":"BMJ","issue":"10","funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SFO Epidemiology"},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2017,10,5]]},"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Proton 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Population-based study in Sweden (2005\u20132012).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>This study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Exposure\/Intervention<\/jats:title>\n                    <jats:p>Maintenance 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome measures<\/jats:title>\n                    <jats:p>Gastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 797\u2009067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95%\u2009CI 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%\u2009CI 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%\u2009CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95%\u2009CI 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Long-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2017-017739","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T08:30:31Z","timestamp":1509352231000},"page":"e017739","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":177,"title":["Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden"],"prefix":"10.1136","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-447X","authenticated-orcid":false,"given":"Nele","family":"Brusselaers","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Wahlin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Engstrand","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-5448","authenticated-orcid":false,"given":"Jesper","family":"Lagergren","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden"},{"name":"Division of Cancer Studies, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2017,10,30]]},"reference":[{"key":"2025121514171664000_7.10.e017739.1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.33.9.1166"},{"key":"2025121514171664000_7.10.e017739.2","first-page":"449","article-title":"Meta-analyses: does long-term PPI use increase the risk of gastric premalignant lesions?","volume":"16","author":"Eslami","year":"2013","journal-title":"Arch Iran Med"},{"key":"2025121514171664000_7.10.e017739.3","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-008-0098-4"},{"key":"2025121514171664000_7.10.e017739.4","unstructured":"The World Medicines Situation (WMS) 2011. 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