{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:58:48Z","timestamp":1788555528458,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009663","name":"University Health Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Solid organ transplant recipients (SOTR) face elevated cancer risk due to prolonged immunosuppression. While higher tacrolimus exposure has been linked to de novo malignancies, the dose\u2013response relationship remains unclear, prompting the need for population\u2010level, longitudinal investigations. To quantify the exposure\u2010response relationship between tacrolimus trough level and post\u2010transplant malignancy risk, we used a population\u2010based cohort study using linked administrative healthcare data from Ontario, Canada. All transplant recipients from January 1, 2008 to March 1, 2020 with \u22652 serum tacrolimus levels in the first year post\u2010transplant were included. Cumulative exposure to tacrolimus was treated as a (1) continuous variable, (2) by quartiles of exposure within the first year and (3) as time\u2010varying exposure beyond the first year; incidence of de novo malignancy was investigated using cause\u2010specific and subdistribution Cox regression models. Among the 5178 SOTRs, a total of 318 de novo malignancies (6.1%) and 332 deaths (6.4%) occurred. For every 20% increase in the cumulative tacrolimus trough level in the first year, a heightened risk of malignancy was observed (HR\u2009=\u20091.09, 95% CI: 1.02\u20131.17). For each 20% increase in cumulative tacrolimus trough level after 1 year, the risk of malignancy increased (HR\u2009=\u20091.08 [95% CI: 1.01\u20131.15]). Patients in the highest quartile of cumulative exposure (median 9\u201310\u2009ng\/mL) had a 47% greater risk of malignancy compared to those in the lowest quartile (median 5\u20136\u2009ng\/mL; HR\u2009=\u20091.47 [95% CI: 1.03\u20132.11]). These findings highlight the importance of carefully titrating tacrolimus and avoiding unnecessary prolonged high exposure, particularly during the critical first year post\u2010transplant.<\/jats:p>","DOI":"10.1002\/ijc.70343","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:31:36Z","timestamp":1769668296000},"page":"3152-3160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cumulative exposure to tacrolimus is associated with increased risk of malignancy for solid organ transplant recipients"],"prefix":"10.1002","volume":"158","author":[{"given":"Sergio A.","family":"Acuna","sequence":"first","affiliation":[{"name":"Division of Transplantation, Department of Surgery University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Ajmera Transplant Centre, University Health Network  Toronto Ontario Canada"},{"name":"Division of Gastroenterology and Hepatology McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Jones\u2010Carr","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of Surgery University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Smith","sequence":"additional","affiliation":[{"name":"ICES Western, London Health Sciences Centre Research Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla","family":"Naylor","sequence":"additional","affiliation":[{"name":"ICES Western, London Health Sciences Centre Research Institute  London Ontario Canada"},{"name":"Department of Medicine Western University  London Ontario Canada"},{"name":"Department of Epidemiology &amp; Biostatistics Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bima J.","family":"Hasjim","sequence":"additional","affiliation":[{"name":"Department of Surgery University of California\u2014Irvine  Orange California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Wen","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine and Women's College Research Institute Women's College Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Baxter","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Joseph","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada. Institute of Health Policy, Management and Evaluation, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamatha","family":"Bhat","sequence":"additional","affiliation":[{"name":"Ajmera Transplant Centre, University Health Network  Toronto Ontario Canada"},{"name":"Division of Gastroenterology &amp; Hepatology, Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002650"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2014530"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.14158"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2018.04.025"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27765"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5137"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2024.151494"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000004694"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0000000000000760"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2018.07.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)08496-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13018"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.17021"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.9778\/cmajo.20190065"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1404"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16318"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001192"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002760"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2017.09.019"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1634956"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2102953"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1204166"},{"key":"e_1_2_10_24_1","volume-title":"Tumour site concordance and mechanisms of carcinogenesised","author":"Rice JM","year":"2019"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000003773"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0000000000000545"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0012.2009.01143.x"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70343","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70343","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:04:54Z","timestamp":1777439094000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,6,15]]}},"alternative-id":["10.1002\/ijc.70343"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70343","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"2025-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}