{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:16:54Z","timestamp":1787318214680,"version":"build-2736575974"},"reference-count":96,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gamma\u2010glutamyl transferase (GGT) has been shown to have associations with several diseases including cancers. Previous studies have investigated the effect of GGT levels on the gastrointestinal (GI) cancer incidence. We aim to systematically investigate these studies to provide better insights into the interrelationship between GGT and GI cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Online databases were searched to find relevant studies investigating different GGT levels' effects on the incidence of GI cancers including colorectal, esophageal, liver, pancreas, gastric, and biliary duct cancers. Random\u2010effect meta\u2010analysis was conducted to pool the hazard ratios (HRs) of GGT quartiles (Qs) effect on cancer incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 26 studies were included in the final review, 12 of which underwent meta\u2010analysis that investigated 11 million patients. Based on the meta\u2010analysis, Q4 patients had a 69% higher hazard of GI cancer incidence (HR 1.69, 95% CI 1.41\u20132.02,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value &lt;\u20090.001). The hazard ratio significance was also similar for Q3 (HR 1.22, 95% CI 1.15\u20131.30,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value &lt;\u20090.001) and Q2 (HR 1.10, 95% CI 1.05\u20131.16,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value =0.002) of GGT. Colorectal and liver cancers showed a higher hazard ratio among Q2, Q3, and Q4 of GGT compared to Q1. In pancreas and bile duct cancers, only Q4 of GGT had significantly higher HR. Q3 and Q4 of GGT levels had statistically significant associations with gastric cancer incidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Higher GGT levels correlate with higher rates of GI cancer incidence, especially in colorectal and hepatic cancers. Future studies should investigate this biomarker's potential role in risk assessment for digestive cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70581","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T06:26:47Z","timestamp":1737008807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Association Between Serum Gamma\u2010Glutamyl Transferase and Gastrointestinal Cancer Risk: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8247-4258","authenticated-orcid":false,"given":"Alireza","family":"Ramandi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Weill Cornell Medicine  New York New York USA"},{"name":"Digestive Disease Research Center Digestive Disease Research Institute, Tehran University of Medical Sciences, Shariati Hospital  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"George","sequence":"additional","affiliation":[{"name":"Storr Liver Centre Westmead Institute for Medical Research, Westmead Hospital and University of Sydney  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-4227","authenticated-orcid":false,"given":"Amir Hossein","family":"Behnoush","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Center Digestive Disease Research Institute, Tehran University of Medical Sciences, Shariati Hospital  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Delavari","sequence":"additional","affiliation":[{"name":"Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Poustchi","sequence":"additional","affiliation":[{"name":"Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-6335","authenticated-orcid":false,"given":"Reza","family":"Malekzadeh","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Center Digestive Disease Research Institute, Tehran University of Medical Sciences, Shariati Hospital  Tehran Iran"},{"name":"Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/20014091084227"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.081620"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.18433\/jpps30923"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.152298"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.06.034"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.06.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2007.10.015"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.552547"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.01.019"},{"issue":"3","key":"e_1_2_12_11_1","first-page":"237","article-title":"Study of Re\u2010Transplantation and Prognosis in Liver Transplant Center in Iran","volume":"14","author":"Salimi J.","year":"2021","journal-title":"Gastroenterology and Hepatology from Bed to Bench"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23714"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.03.010"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29659"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29084"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1343"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2015.02.001"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-014-0370-x"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-013-0251-8"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/CEJ.0000000000000369"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-018-0882-z"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-19-0447"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.917961"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210863"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.4178\/epih.e2020004"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-04231-7_4"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19981230)17:24<2815::AID-SIM110>3.0.CO;2-8"},{"key":"e_1_2_12_29_1","volume-title":"The Newcastle\u2010Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta\u2010Analyses","author":"Wells G. A. S. B.","year":"2014"},{"key":"e_1_2_12_30_1","volume-title":"Meta\u2010Analysis in R","author":"KS L. G. A. J. B.","year":"2023"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1482"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1009"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-21416-0"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001666"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000015987"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2000.00455.x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155342"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8494076"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.12.029"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24356"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-25970-0"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177053"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/osp4.484"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33351"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0245052"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22320"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/CEJ.0b013e3282fa9edd"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000212088"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-033532"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i2.176"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5556"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-009-9499-4"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11092466"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2016.345"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158066"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2016.01.002"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6686"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.2188\/jea.JE20110071"},{"key":"e_1_2_12_61_1","first-page":"13","article-title":"Risk Factor Analysis and Construction of Prediction Models of Gallbladder Carcinoma in Patients With Gallstones. Frontiers","volume":"13","author":"Zhu Z.","year":"2023","journal-title":"Oncology"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(06)74018-3"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.08.027"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802502"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000148324.63685.6a"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.382"},{"issue":"11","key":"e_1_2_12_67_1","first-page":"E2096","article-title":"Structural Basis of Autoregulatory Scaffolding by Apoptosis Signal\u2010Regulating Kinase 1","volume":"114","author":"Weijman J. F.","year":"2017","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22393"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6378"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1359152"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2022.0119"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32083"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI128289"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-023-03540-1"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.355"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.021"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.030"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200209098"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120509"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(02)00174-X"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21670"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/818570"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-9-87"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-016-1212-2"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i45.7109"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-009-9217-7"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.276089"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113657"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2016.6833"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.522"},{"issue":"1","key":"e_1_2_12_91_1","first-page":"53","article-title":"Role of Gamma\u2010Glutamyltransferase in Cardiovascular Diseases","volume":"18","author":"Jiang S.","year":"2013","journal-title":"Experimental and Clinical Cardiology"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1177\/10732748241251712"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.11.312"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.4_suppl.71"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyp161"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-023-10542-9"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.3102\/10769986006002107"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.70581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T18:11:31Z","timestamp":1744913491000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.70581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":96,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/cam4.70581"],"URL":"https:\/\/doi.org\/10.1002\/cam4.70581","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70581"}}