伊立替康致3～4级中性粒细胞减少与UGT1A1基因多态性相关性的Meta分析

发布时间：2018-05-04 09:45

  本文选题：伊立替康 + UGTA基因多态性　； 参考：《中国药房》2017年18期

【摘要】：目的:系统评价UGT1A1基因多态性与伊立替康致3~4级中性粒细胞减少不良反应的相关性,为临床提供循证参考。方法:计算机检索中国期刊全文数据库、万方数据库、中文科技期刊数据库、Pub Med、EMBase、Science direct与Cochrane图书馆,收集UGT1A1*28和UGT1A1*6基因多态性与伊立替康致3~4级中性粒细胞减少的相关研究,对符合纳入标准的研究进行提取资料和质量评价,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入29项研究,合计2 408例患者。UGT1A1*28基因型分为野生型TA 6/6(UGT1A1*1/*1)和突变型TA 6/7(UGT1A1*1/*28)、TA 7/7(UGT1A1*28/*28),UGT1A1*6基因型分为野生型GG和突变型GA、AA。Meta分析结果显示,UGT1A1*28和UGT1A1*6突变型患者3~4级中性粒细胞减少发生率显著高于野生型,差异有统计学意义[UGT1A1*28:OR=1.92,95%CI(1.52,2.44),P0.001;UGT1A1*6:OR=2.49,95%CI(1.46,4.26),P0.001];伊立替康中、高剂量时UGT1A1*28和UGT1A1*6突变型患者3~4级中性粒细胞减少发生率显著高于野生型,差异有统计学意义[UGT1A1*28:OR=2.06,95%CI(1.57,2.70),P0.001);UGT1A1*6:OR=1.92,95%CI(1.35,2.74),P0.001];而伊立替康低剂量时UGT1A1*28和UGT1A1*6突变型患者3~4级中性粒细胞减少发生率与野生型比较差异无统计学意义[UGT1A1*28:OR=1.20,95%CI(0.70,2.08),P=0.51;UGT1A1*6:OR=3.19,95%CI(0.85,11.89),P=0.08]。结论:伊立替康的中、高剂量使用时,UGT1A1*28和UGT1A1*6突变基因会增加肿瘤患者重度中性粒细胞减少风险;但在低剂量时,基因多态性与中性粒细胞减少的相关性无明确的相关性。
[Abstract]:Objective: to evaluate the relationship between the polymorphism of UGT1A1 gene and the adverse reaction of neutrophilic granulocytopenia 3 grade 4 induced by irinotecan in order to provide evidence-based reference for clinical practice. Methods: the full text database of Chinese periodicals, Wanfang database, Chinese scientific journal database Pub MedEMBaseScience direct and Cochrane library were searched by computer. The correlation between UGT1A1*28 and UGT1A1*6 gene polymorphisms and 34 grade neutropenia induced by irinotecan was collected. The data were extracted and the quality was evaluated by using Rev Man 5.3 statistical software for Meta analysis. Results: a total of 29 studies were included, A total of 2 408 patients were divided into wild-type TA6 / 6 UGT1A1A1A1t1 / 1 / 1 and mutant TA6 / 7 UGT1A1A1A1 / 1 / 1 / 7 / 7 UGT1A1A1 / 7 / 7 / 7 UGT1A1 / 28 / UGT1A16 genotype. The results of meta-analysis showed that the incidence of neutropenia was significantly higher in UGT1A1A128 and UGT1A1*6 mutant patients than in wild-type GG and mutant GG and UGT1A1*6 mutant patients with 34 grades of neutrophilic granulocytopenia. The difference was statistically significant [UGT1A1 / 28: OR1: 1.92C95: CI1. 52 / 2.44 / P0.001 / UGT1A1 / 6: 2.49 / 95CI1.46 / 4.26 / P0.001], the incidence of grade 34 neutropenia in patients with UGT1A1*28 and UGT1A1*6 mutation at high doses was significantly higher than that in wild-type patients, and the rate of neutropenia was significantly higher in Iritecan patients than in wild-type patients. 宸�寮傛湁缁熻�″�︽剰涔塠UGT1A1*28:OR=2.06,95%CI(1.57,2.70),P0.001);UGT1A1*6:OR=1.92,95%CI(1.35,2.74),P0.001];鑰屼紛绔嬫浛搴蜂綆鍓傞噺鏃禪GT1A1*28鍜孶GT1A1*6绐佸彉鍨嬫偅鑰，

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