{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T19:44:48Z","timestamp":1767642288864,"version":"3.48.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["RGP1\/11\/46"],"award-info":[{"award-number":["RGP1\/11\/46"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ir J Med Sci"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s11845-025-04085-1","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T09:11:34Z","timestamp":1757754694000},"page":"2095-2104","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ecological associations between gastric acid suppressant use and gastrointestinal cancer incidence: a three-decade global study"],"prefix":"10.1007","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6651-2306","authenticated-orcid":false,"given":"Khalid","family":"Orayj","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"4085_CR1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1007\/s00228-023-03534-z","volume":"79","author":"LGT Shanika","year":"2023","unstructured":"Shanika LGT, Reynolds A, Pattison S, Braund R (2023) Proton pump inhibitor use: systematic review of global trends and practices. Eur J Clin Pharmacol 79:1159\u20131172. https:\/\/doi.org\/10.1007\/s00228-023-03534-z","journal-title":"Eur J Clin Pharmacol"},{"key":"4085_CR2","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-2803.24612023-153","volume":"61","author":"JF Pi\u00f1er\u00faa-Gons\u00e1lvez","year":"2024","unstructured":"Pi\u00f1er\u00faa-Gons\u00e1lvez JF, Zambrano-Infantino RDC, Albornoz-Sandoval JC et al (2024) Behind the proton pump inhibitor prescription: an international survey on physician practices and knowledge. Arq Gastroenterol 61:e23153. https:\/\/doi.org\/10.1590\/S0004-2803.24612023-153","journal-title":"Arq Gastroenterol"},{"key":"4085_CR3","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.ejca.2021.07.030","volume":"156","author":"R Zeng","year":"2021","unstructured":"Zeng R, Cheng Y, Luo D et al (2021) Comprehensive analysis of proton pump inhibitors and risk of digestive tract cancers. Eur J Cancer 156:190\u2013201. https:\/\/doi.org\/10.1016\/j.ejca.2021.07.030","journal-title":"Eur J Cancer"},{"key":"4085_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.979215","volume":"13","author":"W Zhou","year":"2022","unstructured":"Zhou W, Chen X, Fan Q et al (2022) Using proton pump inhibitors increases the risk of hepato-biliary-pancreatic cancer. A systematic review and meta-analysis. Front Pharmacol 13:979215. https:\/\/doi.org\/10.3389\/fphar.2022.979215","journal-title":"Front Pharmacol"},{"key":"4085_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13071970","volume":"13","author":"IO Sawaid","year":"2024","unstructured":"Sawaid IO, Samson AO (2024) Proton pump inhibitors and cancer risk: a comprehensive review of epidemiological and mechanistic evidence. J Clin Med 13:1970. https:\/\/doi.org\/10.3390\/jcm13071970","journal-title":"J Clin Med"},{"key":"4085_CR6","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1080\/17474124.2023.2204229","volume":"17","author":"A Choudhury","year":"2023","unstructured":"Choudhury A, Jena A, Jearth V et al (2023) Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 17:479\u2013487. https:\/\/doi.org\/10.1080\/17474124.2023.2204229","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"4085_CR7","unstructured":"OECD (2025) OECD Health Statistics 2024. In: OECD Health Statistics 2024"},{"key":"4085_CR8","unstructured":"IHME (2025) Global Burden of Disease Study 2019 (GBD 2019) data resources. In: Global Burden of Disease Study 2019 (GBD 2019) Data Resources"},{"key":"4085_CR9","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v4.i7.156","volume":"4","author":"S Nagini","year":"2012","unstructured":"Nagini S (2012) Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 4:156. https:\/\/doi.org\/10.4251\/wjgo.v4.i7.156","journal-title":"World J Gastrointest Oncol"},{"key":"4085_CR10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/sj.bjc.6606032","volume":"104","author":"TJ Key","year":"2011","unstructured":"Key TJ (2011) Fruit and vegetables and cancer risk. Br J Cancer 104:6\u201311. https:\/\/doi.org\/10.1038\/sj.bjc.6606032","journal-title":"Br J Cancer"},{"key":"4085_CR11","unstructured":"World Bank Group (2025) World bank open data [Internet]. Washington, DC: The World Bank. Available from: https:\/\/data.worldbank.org. Accessed 11 June 2025"},{"key":"4085_CR12","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1136\/bmj.316.7139.1236","volume":"316","author":"TV Perneger","year":"1998","unstructured":"Perneger TV (1998) What\u2019s wrong with Bonferroni adjustments. BMJ 316:1236\u20131238. https:\/\/doi.org\/10.1136\/bmj.316.7139.1236","journal-title":"BMJ"},{"key":"4085_CR13","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3892\/ol.2023.14161","volume":"27","author":"TH Tran","year":"2024","unstructured":"Tran TH, Myung S-K, Trinh TTK (2024) Proton pump inhibitors and risk of gastrointestinal cancer: a meta-analysis of cohort studies. Oncol Lett 27:28. https:\/\/doi.org\/10.3892\/ol.2023.14161","journal-title":"Oncol Lett"},{"key":"4085_CR14","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1097\/COC.0000000000000949","volume":"45","author":"M-L Zhang","year":"2022","unstructured":"Zhang M-L, Fan Y-X, Meng R et al (2022) Proton pump inhibitors and cancer risk: an umbrella review and meta-analysis of observational studies. Am J Clin Oncol 45:475\u2013485. https:\/\/doi.org\/10.1097\/COC.0000000000000949","journal-title":"Am J Clin Oncol"},{"key":"4085_CR15","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000036085","volume":"102","author":"R Zhao","year":"2023","unstructured":"Zhao R, Lin S, Han M et al (2023) Does proton pump inhibitors use increase risk of digestive tumors?: A 2-sample Mendelian randomization study. Medicine (Baltimore) 102:e36085. https:\/\/doi.org\/10.1097\/MD.0000000000036085","journal-title":"Medicine (Baltimore)"},{"key":"4085_CR16","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1053\/j.gastro.2007.06.014","volume":"133","author":"DJ Robertson","year":"2007","unstructured":"Robertson DJ, Larsson H, Friis S et al (2007) Proton pump inhibitor use and risk of colorectal cancer: a population-based, case-control study. Gastroenterology 133:755\u2013760. https:\/\/doi.org\/10.1053\/j.gastro.2007.06.014","journal-title":"Gastroenterology"},{"issue":"22","key":"4085_CR17","doi-asserted-by":"publisher","first-page":"6817","DOI":"10.3748\/wjg.v21.i22.6817","volume":"21","author":"S Fujimori","year":"2015","unstructured":"Fujimori S (2015) What are the effects of proton pump inhibitors on the small intestine? World J Gastroenterol 21(22):6817\u20136819. https:\/\/doi.org\/10.3748\/wjg.v21.i22.6817","journal-title":"World J Gastroenterol"},{"key":"4085_CR18","doi-asserted-by":"publisher","first-page":"448","DOI":"10.5056\/jnm21177","volume":"27","author":"KB Bang","year":"2021","unstructured":"Bang KB (2021) Risk of pyogenic liver abscess in proton pump inhibitor users: new inventory of proton pump inhibitor induced complications? J Neurogastroenterol Motil 27:448\u2013450. https:\/\/doi.org\/10.5056\/jnm21177","journal-title":"J Neurogastroenterol Motil"},{"key":"4085_CR19","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1111\/apt.14841","volume":"48","author":"HL Waldum","year":"2018","unstructured":"Waldum HL (2018) Editorial: proton pump inhibitors (PPIs) and primary liver cancer. Aliment Pharmacol Ther 48:380\u2013381. https:\/\/doi.org\/10.1111\/apt.14841","journal-title":"Aliment Pharmacol Ther"},{"key":"4085_CR20","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1007\/s00228-020-02854-8","volume":"76","author":"HJ Song","year":"2020","unstructured":"Song HJ, Jiang X, Henry L et al (2020) Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis. Eur J Clin Pharmacol 76:851\u2013866. https:\/\/doi.org\/10.1007\/s00228-020-02854-8","journal-title":"Eur J Clin Pharmacol"},{"key":"4085_CR21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1080\/17425255.2023.2190883","volume":"19","author":"R Chevalier","year":"2023","unstructured":"Chevalier R, Attard T, Van Driest SL, Shakhnovich V (2023) A fresh look at proton pump inhibitor (PPI)-associated adverse events through a CYP2C19 pharmacogenetic lens. Expert Opin Drug Metab Toxicol 19:53\u201356. https:\/\/doi.org\/10.1080\/17425255.2023.2190883","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"4085_CR22","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s00535-021-01764-5","volume":"56","author":"S-W Lai","year":"2021","unstructured":"Lai S-W (2021) Proton pump inhibitors and the risk of pancreatic cancer. J Gastroenterol 56:293\u2013294. https:\/\/doi.org\/10.1007\/s00535-021-01764-5","journal-title":"J Gastroenterol"},{"key":"4085_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.798272","volume":"13","author":"M Bridoux","year":"2022","unstructured":"Bridoux M, Simon N, Turpin A (2022) Proton pump inhibitors and cancer: current state of play. Front Pharmacol 13:798272. https:\/\/doi.org\/10.3389\/fphar.2022.798272","journal-title":"Front Pharmacol"},{"key":"4085_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14215357","volume":"14","author":"TN Poly","year":"2022","unstructured":"Poly TN, Islam MM, Walther BA et al (2022) Proton pump inhibitors use and the risk of pancreatic cancer: evidence from eleven epidemiological studies, comprising 1.5 million individuals. Cancers (Basel) 14:215357. https:\/\/doi.org\/10.3390\/cancers14215357","journal-title":"Cancers (Basel)"},{"key":"4085_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082220","author":"H-E Hong","year":"2020","unstructured":"Hong H-E, Kim A-S, Kim M-R et al (2020) Does the use of proton pump inhibitors increase the risk of pancreatic cancer? A systematic review and meta-analysis of epidemiologic studies. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers12082220","journal-title":"Cancers (Basel)"},{"key":"4085_CR26","doi-asserted-by":"publisher","first-page":"706","DOI":"10.14309\/ajg.0000000000000591","volume":"115","author":"JK Lee","year":"2020","unstructured":"Lee JK, Merchant SA, Schneider JL et al (2020) Proton pump inhibitor use and risk of gastric, colorectal, liver, and pancreatic cancers in a community-based population. Am J Gastroenterol 115:706\u2013715. https:\/\/doi.org\/10.14309\/ajg.0000000000000591","journal-title":"Am J Gastroenterol"},{"key":"4085_CR27","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/S1470-2045(09)70035-X","volume":"10","author":"J Cuzick","year":"2009","unstructured":"Cuzick J, Otto F, Baron JA et al (2009) Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 10:501\u2013507. https:\/\/doi.org\/10.1016\/S1470-2045(09)70035-X","journal-title":"Lancet Oncol"},{"key":"4085_CR28","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3109\/00365529609094766","volume":"220","author":"HA Weiss","year":"1996","unstructured":"Weiss HA, Forman D (1996) Aspirin, non-steroidal anti-inflammatory drugs and protection from colorectal cancer: a review of the epidemiological evidence. Scand J Gastroenterol Suppl 220:137\u2013141. https:\/\/doi.org\/10.3109\/00365529609094766","journal-title":"Scand J Gastroenterol Suppl"},{"key":"4085_CR29","doi-asserted-by":"publisher","first-page":"3018","DOI":"10.1111\/cas.14149","volume":"110","author":"S Umezawa","year":"2019","unstructured":"Umezawa S, Higurashi T, Komiya Y et al (2019) Chemoprevention of colorectal cancer: past, present, and future. Cancer Sci 110:3018\u20133026. https:\/\/doi.org\/10.1111\/cas.14149","journal-title":"Cancer Sci"},{"key":"4085_CR30","first-page":"241","volume":"24","author":"T Hanaoka","year":"1994","unstructured":"Hanaoka T, Tsugane S, Ando N et al (1994) Alcohol consumption and risk of esophageal cancer in Japan: a case-control study in seven hospitals. Jpn J Clin Oncol 24:241\u2013246","journal-title":"Jpn J Clin Oncol"},{"key":"4085_CR31","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/s0899-9007(03)00146-1","volume":"19","author":"L Ke","year":"2003","unstructured":"Ke L, Ping Y, Ge H (2003) Protective action of fresh fruit and vegetable consumption on the synergic effect of alcohol and tobacco use on esophageal cancer in South China. Nutrition 19:821. https:\/\/doi.org\/10.1016\/s0899-9007(03)00146-1","journal-title":"Nutrition"},{"key":"4085_CR32","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1093\/ije\/dyn356","volume":"38","author":"JM Oakes","year":"2009","unstructured":"Oakes JM (2009) Commentary: individual, ecological and multilevel fallacies. Int J Epidemiol 38:361\u2013368. https:\/\/doi.org\/10.1093\/ije\/dyn356","journal-title":"Int J Epidemiol"},{"key":"4085_CR33","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1088\/0952-4746\/22\/2\/302","volume":"22","author":"JH Lubin","year":"2002","unstructured":"Lubin JH (2002) The potential for bias in Cohen\u2019s ecological analysis of lung cancer and residential radon. J Radiol Prot 22:141\u2013148. https:\/\/doi.org\/10.1088\/0952-4746\/22\/2\/302","journal-title":"J Radiol Prot"},{"key":"4085_CR34","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.wneu.2015.05.002","volume":"84","author":"EG Figueiredo","year":"2015","unstructured":"Figueiredo EG, Teixeira MJ (2015) Cancer etiology, bad luck, and ecological fallacy. World Neurosurg 84:20. https:\/\/doi.org\/10.1016\/j.wneu.2015.05.002","journal-title":"World Neurosurg"},{"key":"4085_CR35","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1158\/1055-9965.EPI-17-1177","volume":"27","author":"J Yarmolinsky","year":"2018","unstructured":"Yarmolinsky J, Wade KH, Richmond RC et al (2018) Causal inference in cancer epidemiology: what is the role of Mendelian randomization? Cancer Epidemiol Biomarkers Prev 27:995\u20131010. https:\/\/doi.org\/10.1158\/1055-9965.EPI-17-1177","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"4085_CR36","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.14309\/ajg.0000000000002826","volume":"119","author":"GC Meine","year":"2024","unstructured":"Meine GC, Picon RV, Esp\u00edrito Santo PA, Sander GB (2024) Ultra-processed food consumption and gastrointestinal cancer risk: a systematic review and meta-analysis. Am J Gastroenterol 119:1056\u20131065. https:\/\/doi.org\/10.14309\/ajg.0000000000002826","journal-title":"Am J Gastroenterol"}],"container-title":["Irish Journal of Medical Science (1971 -)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11845-025-04085-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11845-025-04085-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11845-025-04085-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T16:30:51Z","timestamp":1767630651000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11845-025-04085-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,13]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["4085"],"URL":"https:\/\/doi.org\/10.1007\/s11845-025-04085-1","relation":{},"ISSN":["0021-1265","1863-4362"],"issn-type":[{"type":"print","value":"0021-1265"},{"type":"electronic","value":"1863-4362"}],"subject":[],"published":{"date-parts":[[2025,9,13]]},"assertion":[{"value":"11 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This research analyzed only aggregate, publicly available data from international databases and did not involve any human participants or animals. According to institutional and national guidelines, no ethics committee approval was required for this type of study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable (no human participants were involved in the study).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable (the study does not include any individual person\u2019s data).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author declares no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}