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
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篇名: | 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 |
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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、PubMed、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),P<0.001;UGT1A1*6:OR=2.49,95%CI(1.46,4.26),P<0.001];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),P<0.001);UGT1A1*6: OR=1.92,95%CI(1.35,2.74),P<0.001];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 association between UGT1A1 gene polymorphism and irinotecan-induced 3-4 degree neutropenia, and to provide evidenced-based reference for clinical treatment. METHODS: Retrieved from CJFD, Wanfang database, VIP, PubMed, EMBase, Science direct and Cochrane library, related studies about UGT1A1*28 and UGT1A1*6 gene polymorphism and irinotecan-induced 3-4 degree neutropenia were collected. After data extraction and quality evaluation of included studies, Meta-analysis was conducted by using Review Man 5.3 software. RESULTS: A total of 29 studies were included, involving 2 408 patients. UGT1A1*28 includ wild genotype TA 6/6(UGT1A1*1/*1)and mutations genotype TA 6/7(UGT1A1*1/*28)、TA 7/7(UGT1A1*28/*28),UGT1A1*6 includ wild genotype GG and mutations genotype GA、AA. Results of Meta-analysis showed: the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype, with statistical significance [UGT1A1*28:OR=1.92,95%CI(1.52,2.44),P<0.001; UGT1A1*6:OR=2.49,95%CI(1.46,4.26),P<0.001]. Using medium-dose and high-dose of irinotecan, the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype, with statistical significance [UGT1A1*28:OR=2.06,95%CI(1.57,2.70),P<0.001);UGT1A1*6:OR=1.92,95%CI(1.35,2.74),P<0.001]. Using low-dose of irinotecan, there was no statistical significance in the incidence of 3-4 degree neutropenia between UGT1A1*28, UGT1A1*6 mutations genotype and wild genotype [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]. CONCLUSIONS: Using medium-dose and high-dose of irinotecan, UGT1A1*28 and UGT1A1*6 mutations will increase the risk of severe neutropenia in cancer patients. Using low-dose of irinotecan, there is no clear correlation between gene polymorphism and the neutropenia. |
期刊: | 2017年第28卷第18期 |
作者: | 印亚双,王培香,段京莉 |
AUTHORS: | YIN Yashuang,WANG Peixiang,DUAN Jingli |
关键字: | 伊立替康;UGT1A1基因多态性;中性粒细胞减少;Meta分析 |
KEYWORDS: | Irinotecan; UGT1A1 gene polymorphism; Neutropenia; Meta-analysis |
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