中国病理生理杂志2012，Vol.28Issue(5)：823-828,6.DOI:10.3969/j.issn.1000-4718.2012.05.010
UGT1A1基因多态性与转移性结直肠癌伊立替康化疗毒性及疗效的关系
Relationship between UGT1A1 gene polymorphisms and toxicity/efficacy of irinotecan-based chemotherapy in metastatic colorectal cancer
摘要
Abstract
AIM: To invesligale the correlation of UGT1A1 * 28 and UGT1A1 * 6 gene polymorphisms with irino-tecan - associated adverse evenls and efficacy in the palienls with metastatic colorectal cancer (mCRC) trealed with irinole-can - based chemolherapy. METHODS: Analysis of UGT1A1 * 28 and UGT1A1 * 6 gene polymorphisms was performed in 207 gaslroinleslinal cancer palienls admilled to our hospital from April 2010 to March 2012 by amplifying the gene frag-ments using PCR and direcl sequencing. Fifty six cases wilh mCRC trealed wilh irinolecan were chosen lo observe the adverse evenls and efficacy during chemolherapy, and the lime lo progression (TTP) was also recorded. The incidence of dif-ferenl genolypes was compared. RESULTS: The distribution of the genolypes in 207 gaslroinleslinal cancer palienls was as follows: UGT1A1 * 28 wild - type ( WT) genolype TA6/6 ( 164 , 79. 2% ) , helerozygous genolype TA6/7 (41, 19.8%), and homozygous genolype TA7/7 (2, 1. 0% ) ; UGT1A1 * 6 WT genolype G/G ( 154, 74. 4% ) , helerozygous genolype G/ A (51, 24.6%), and homozygous genolype A/A (2, 1.0%). In the 56 mCRC cases, the incidence of grade 3 and 4 delayed diarrhea and neulropenia in the palienls carrying UGT1A1 *6 ( G/A and A/A) was higher than that in the WT genolype (6/6) (38.9% vs 7.9% ,61. 1% vs 29.0% , both P<0.05). The incidence of grade 3 and 4 thrombocylopenia in the palienls carrying UGTIAI* 28 (TA6/7 and TA7/7) was higher lhan lhal in the WT genolype (TA6/6) (33.3% vs 2. 1 % , P < 0. 05 ) . No significant difference of TTP and chemotherapeutic effect was observed belween different genotypes. CONCLUSION: The UGT1A1 * 6 ( G/A and A/A) genolypes increase the risk of grade 3 and 4 delayed diarrhea and neu-tropenia, and the UGT1A1*28 (TA6/7 and TA7/7 ) genolypes increase the risk of grade 3 and 4 thrombocylopenia in mCRC palients trealed with irinolecan - based chemotherapy.关键词
伊立替康/结直肠肿瘤/基因,UGT1A1/基因多态性Key words
Irinolecan/ Coloreclal neoplasms/ Genes, UGT1A1/ Genelic polymorphism分类
医药卫生引用本文复制引用
张君孝,王晨亮,黄美近,傅新晖,卢碧燕,邓艳红,刘焕亮..UGT1A1基因多态性与转移性结直肠癌伊立替康化疗毒性及疗效的关系[J].中国病理生理杂志,2012,28(5):823-828,6.基金项目
广州市科技计划项目(No.2011J5200009) （No.2011J5200009）
中山大学百人计划科研团队建设项目(No.88000-3281302) （No.88000-3281302）
辉瑞制药与中山大学胃肠病学研究所合作项目(横向) （横向）
