Dose-dependent association between UGT1A1*28 polymorphism and irinotecan-induced diarrhoea: A meta-analysis

doi:10.1016/j.ejca.2010.02.049

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	*Dose-dependent association between UGT1A128 polymorphism and irinotecan-induced diarrhoea: A meta-analysis**
	Hu, Zhe-Yi 2,3; Yu, Qj 1; Zhao, Yuan-Sheng 2,3
刊名	EUROPEAN JOURNAL OF CANCER
	2010-07
卷号	46 期号:10 页码:1856-1865
关键词	Meta-analysis UGT1A1*28 Irinotecan Diarrhoea
ISSN号	0959-8049
DOI	10.1016/j.ejca.2010.02.049
文献子类	Article
英文摘要	Life-threatening diarrhoea is observed in up to 25% of cancer patients receiving irinotecan. The associations between the UGT1A128 polymorphism and irinotecan-induced diarrhoea remains controversial because of conflicting data in the literature. Meta-analyses were performed on published data in terms of relationships between UGT1A128 and severe diarrhoea. We searched databases for relevant studies that were published in English or Chinese. Two reviewers extracted data and assessed methodological quality. UGT1A128 related odds ratios (ORs) were pooled by use of a fixed-effects model. The studies included were stratified into subgroups representing different races and irinotecan doses, and meta-regression analyses were performed to investigate the effect of study characteristics on the association between UGT1A128 and diarrhoea. Twenty trials including a total of 1760 cancer patients were included. The risk of severe diarrhoea at medium and high irinotecan doses was higher among patients with a UGT1A128/28 genotype than among those with a UGT1A11/1 genotype (OR = 3.69, 95% confidence interval [CI] = 2.00-6.83; P < 0.001). Considering the patients with a UGT1A11/28 genotype, the risk of toxicity was also higher than among those with a wild-type genotype at medium and high doses (OR = 1.92, 95% CI = 1.31-2.82; P = 0.001). No association was observed between UGT1A128 and severe diarrhoea at low doses (<125 mg/m(2)). In conclusion, patients carrying UGT1A128 allele(s) are at an increased risk of irinotecan-induced severe diarrhoea. This increased risk is only apparent in those who are administrated with medium or high irinotecan doses. (C) 2010 Elsevier Ltd. All rights reserved.
WOS关键词	METASTATIC COLORECTAL-CANCER ; CELL LUNG-CANCER ; GASTROINTESTINAL TOXICITY ; UGT1A1 POLYMORPHISM ; INDUCED NEUTROPENIA ; GENETIC-VARIANTS ; PHARMACOKINETICS ; GENOTYPE ; 1A1 ; GLUCURONIDATION
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000280035500027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278854]
专题	上海药物代谢研究中心
通讯作者	Hu, Zhe-Yi
作者单位	1.Shanghai Jiao Tong Univ, Dept Pharm & Clin Pharmacol, Peoples Hosp 6, Shanghai 200233, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Hu, Zhe-Yi,Yu, Qj,Zhao, Yuan-Sheng. Dose-dependent association between UGT1A1*28 polymorphism and irinotecan-induced diarrhoea: A meta-analysis[J]. EUROPEAN JOURNAL OF CANCER,2010,46(10):1856-1865.
APA	Hu, Zhe-Yi,Yu, Qj,&Zhao, Yuan-Sheng.(2010).Dose-dependent association between UGT1A1*28 polymorphism and irinotecan-induced diarrhoea: A meta-analysis.EUROPEAN JOURNAL OF CANCER,46(10),1856-1865.
MLA	Hu, Zhe-Yi,et al."Dose-dependent association between UGT1A1*28 polymorphism and irinotecan-induced diarrhoea: A meta-analysis".EUROPEAN JOURNAL OF CANCER 46.10(2010):1856-1865.