title: Prolonged neutropenia after irinotecan-based chemotherapy in a child with polymorphisms of UGT1A1 and SLCO1B1.
abstract: Genetic polymorphisms of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and SLCO1B1 coding organic anion-transporter polypeptide 1B1, are independent risk factors known to increase irinotecan toxicity in adults. Although combined occurrence of polymorphisms in these 2 genes is likely to influence susceptibility to irinotecan toxicity, data are scarce, especially in children. We report an 11-year-old female with severe and prolonged neutropenia after irinotecan-based chemotherapy. The patient's genotyping revealed polymorphisms in both UGT1A1 and SLCO1B1. To our knowledge, this is the first case report of combined genotyping of both UGT1A1 and SLCO1B1 in a child with severe irinotecan toxicity.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. shinya.ito@sickkids.ca
authors.forename: S
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: F
authors.initials: F
authors.lastname: Garcia-Bournissen
authors.forename: R
authors.initials: R
authors.lastname: Kim
authors.forename: U I
authors.initials: UI
authors.lastname: Schwarz
authors.forename: P C
authors.initials: PC
authors.lastname: Nathan
authors.forename: S
authors.initials: S
authors.lastname: Ito
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D027381:Liver-Specific Organic Anion Transporter 1; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced*; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018232:Rhabdomyosarcoma, Alveolar / Q000188:drug therapy; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D000099148:UGT1A1 Enzyme; C503999:SLCO1B1 protein, human