{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T09:36:52Z","timestamp":1774517812136,"version":"3.50.1"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>Irinotecan treatment is often complicated by gastrointestinal, hematological, and infusion-related toxicities, the latter of which typically presents as acute cholinergic syndrome (ACS). While genetic variation in <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic> increases toxicity risk, fewer studies have investigated variation in other genes. This study aimed to assess the impact of variation in other genes involved in irinotecan pharmacokinetics with irinotecan-related toxicity. This was a retrospective study of patients receiving standard irinotecan doses (180\u2005mg\/m<jats:sup>2<\/jats:sup>) with available genetic and clinical data. The primary analysis was to investigate the impact of carboxylesterase (CES) genetic variation on irinotecan infusion-related ACS. Exploratory secondary analyses evaluated variation in <jats:italic toggle=\"yes\">CES1<\/jats:italic>, <jats:italic toggle=\"yes\">CES2<\/jats:italic>, <jats:italic toggle=\"yes\">UGT1A7<\/jats:italic>, <jats:italic toggle=\"yes\">UGT1A9<\/jats:italic>, <jats:italic toggle=\"yes\">ABCB1<\/jats:italic>, <jats:italic toggle=\"yes\">ABCG2<\/jats:italic>, <jats:italic toggle=\"yes\">ABCC2<\/jats:italic>, and <jats:italic toggle=\"yes\">SLCO1B1<\/jats:italic> with severe toxicity, treatment modification, diarrhea, and neutropenia. Univariate associations with <jats:italic toggle=\"yes\">P<\/jats:italic> less than 0.05 were adjusted for <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic>*28 and <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic>*6 genotype. A total of 93 patients were included in this analysis. <jats:italic toggle=\"yes\">CES1<\/jats:italic> variants were not associated with infusion-related ACS. In the exploratory analysis, <jats:italic toggle=\"yes\">CES1<\/jats:italic> rs3785161 AA was associated with an increased likelihood of severe irinotecan toxicity (37 vs. 16%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2005=\u20050.034), and <jats:italic toggle=\"yes\">ABCG2<\/jats:italic> rs2231142 AA\/AC was associated with an increased likelihood of severe neutropenia (33 vs. 8%; <jats:italic toggle=\"yes\">P<\/jats:italic>\u2005=\u20050.017). <jats:italic toggle=\"yes\">CES1<\/jats:italic> and <jats:italic toggle=\"yes\">ABCG2<\/jats:italic> variants may increase the risk of irinotecan toxicity. Further studies are needed to validate these associations to justify prospective studies investigating the clinical benefits of genetics-guided irinotecan dosing.<\/jats:p>","DOI":"10.1097\/fpc.0000000000000574","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T16:05:49Z","timestamp":1756915549000},"page":"226-231","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Association of genetic variation with irinotecan infusion reactions and severe toxicity"],"prefix":"10.1097","volume":"35","author":[{"given":"Kelly I.","family":"Nugent","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyucheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maisa","family":"Nazzal","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy L.","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel L.","family":"Hertz","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, 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