title: UGT1A1 6/28 polymorphisms could predict irinotecan-induced severe neutropenia not diarrhea in Chinese colorectal cancer patients.
abstract: The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced colorectal cancer patients. The genotypes of UGT1A1 6 and UGT1A1 28 were analyzed by PCR amplification and Sanger sequencing in 276 advanced colorectal cancer patients receiving irinotecan-containing chemotherapy. The influences of UGT1A1 6/28 polymorphisms on severe diarrhea and neutropenia were analyzed. The overall incidence of UGT1A1 6 and UGT1A1 28 variants was 35.5 % (GA: 28.6 %; AA: 6.9 %) and 21.0 % (TA6/TA7: 19.9 %; TA7/TA7: 1.1 %) in our cohort, respectively. A total of 16 patients (5.8 %, 16/276) had severe diarrhea and 56 patients (20.3 %, 56/276) had severe neutropenia. Neither UGT1A1 6 nor UGT1A1 28 variants were associated with severe diarrhea; however, either UGT1A1 6 (P = 0.001) or UGT1A1 28 (P = 0.029) variants were significantly associated with severe neutropenia. No differences were found between severe toxicities and clinical response in this study. Compared to western countries, Chinese patients had a distinct frequency of UGT1A1 6 or UGT1A1 28 genotypes. Both UGT1A1 6 and UGT1A1 28 variants were closely associated with irinotecan-induced severe neutropenia, but not diarrhea.
authors.affiliation: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University, Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Ru
authors.initials: R
authors.lastname: Jia
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D003967:Diarrhea / Q000139:chemically induced / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D009503:Neutropenia / Q000139:chemically induced / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme