NUDT15基因多态性与儿童急性淋巴细胞白血病化疗中6-巯基嘌呤毒性相关性的Meta分析  

Meta-analysis of the association between NUDT15 gene polymorphism and 6-MP toxicity during chemotherapy in childhood acute lymphoblastic leukemia

作　　者：梁麟龙 谭慧仪 刘炀[1] 吴成秋[2] 殷小成[1] Liang Linlong;Tan Huiyi;Liu Yang;Wu Chengqiu;Yin Xiaocheng(Department of Pediatrics,the First Affiliated Hospital of University of South China,Hengyang 421000,China;School of Public Health,University of South China,Hengyang 421000,China)

机构地区：[1]南华大学附属第一医院儿科,衡阳421000 [2]南华大学公共卫生学院,衡阳421000

出　　处：《国际儿科学杂志》2022年第3期208-213,共6页International Journal of Pediatrics

基　　金：湖南省卫健委2020年度科研立项课题(20201977)。

摘　　要：目的系统评价儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患儿中NUDT15基因c.415>C位点多态性与化疗中6-巯基嘌呤(6-mercaptopurine,6-MP)毒性的相关性。方法系统检索国内外相关数据库:PubMed、EmBase、Cochrane Library、中国知网、中国生物医学文献数据库、维普中文科技期刊数据库以及万方数据库,语种限定为中文或英文。纳入符合6-MP治疗儿童ALL关于NUDT15基因c.415>C位点多态性相关毒性的病例对照研究或队列研究,检索时限均为从建库起至2020年10月1日。由两名研究者独立筛选文献,对符合纳入标准的文献进行资料数据提取,并评价纳入研究的文献质量后,应用Rev Man 5.3和Stata12.0软件对不同遗传模型下NUDT15基因c.415>C位点多态性与6-MP化疗过程中毒性的相关性进行Meta分析。结果最终纳入9项研究,8项为队列研究,1项为病例对照研究,共1068例患儿。Meta分析结果表明,在五种遗传模型下NUDT15基因c.415>C位点突变型与白细胞减少及中性粒细胞减少的发生风险均存在显著关联(P均<0.01),而与肝功能损害的发生风险均无显著关联(P均>0.05)。结论NUDT15基因c.415>C位点突变型显著增加了6-MP化疗时白细胞减少及中性粒细胞减少的发生率,但对肝功能损害的发生无明显影响。Objective To evaluate systematically the association between the c.415>C polymorphism of NUDT15 gene and the toxicity of 6-mercaptopurine(6-MP)in children with acute lymphoblastic leukemia(ALL).Methods The literatures in domestic and foreign databases were retrieved:PubMed,EmBase,Cochrane Library,CNKI,CBM,VIP Chinese Sci-tech Journal Database,and Wanfang Database.The language was limited to Chinese or English.A case-control study or cohort study of 6-MP treatment in pediatric ALL related to the toxicity of the NUDT15 gene c.415>C polymorphism was included.The time of search was set from the establishment of the database to October 1st,2020.Two researchers screened the literature independently,extracted data from the literature that met the inclusion criteria,and evaluated the quality of the included studies.The association between locus polymorphism and toxicity during 6-MP chemotherapy was analyzed by Meta analysis with Rev Man 5.3 and Stata 12.0 software.Results Nine studies were finally included,eight of which were cohort studies and one was a case-control study,with a total of 1068 patients.The results showed that under the five genetic models,the mutation at c.415>C of NUDT15 gene was significantly associated with the risk of leukopenia and neutropenia(P<0.01),while hepatotoxicity was with no significant association between the occurrence risk of damage(P>0.05).Conclusion The mutation at c.415>C of NUDT15 gene significantly increased the incidence of leukopenia and neutropenia during 6-MP chemotherapy,while there was no significant effect on the occurrence of hepatotoxicity.

关 键 词：儿童 急性淋巴细胞白血病 NUDT15 6-巯基嘌呤 基因多态性 META分析 

分 类 号：R733.71[医药卫生—肿瘤]