title: UGT1A1*6, UGT1A7*3 and UGT1A9*1b polymorphisms are predictive markers for severe toxicity in patients with metastatic gastrointestinal cancer treated with irinotecan-based regimens.
abstract: Irinotecan-induced severe neutropenia and diarrhea, which remain unpredictable, has restrained the dose and clinical efficiency of irinotecan administration. In the present study, a total of 70 irinotecan-treated patients with histologically confirmed metastatic gastrointestinal cancer were enrolled. Despite genotyping well-reported alleles, direct sequencing was specifically adopted to avoid ethnic heterogeneity and to identify novel variations. The promoter (-1000 bp) and exon 1 regions of UDP glucuronosyltransferase family 1 member A complex locus (UGT1A1) gene family members UGT1A1, UGT1A7 and UGT1A9 were sequenced, and comprehensive analysis of their genetic polymorphisms was performed to determine the association between inherited genetic variations and irinotecan-induced toxicity. A total of 23 different genetic variants were detected in the present study, including 2 novel polymorphisms. The results of the present study revealed that UGT1A1*6 and UGT1A7*3 are risk factors for irinotecan-induced severe neutropenia, and UGT1A9*1b is associated with severe diarrhea. These results may provide biomarkers for the selection of the optimal chemotherapy for Chinese patients with metastatic gastrointestinal cancer.
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.
authors.forename: Chengxu
authors.initials: C
authors.lastname: Cui
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Cao
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.
authors.forename: Junbao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zou
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Songnian
authors.initials: S
authors.lastname: Hu
keywords: UGT1A; diarrhea; irinotecan; neutropenia; polymorphisms