晚期非小细胞肺癌患者XPD基因多态性与铂类药物化疗临床疗效相关性的Meta分析
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篇名: 晚期非小细胞肺癌患者XPD基因多态性与铂类药物化疗临床疗效相关性的Meta分析
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摘要: 目的:系统评价晚期非小细胞肺癌(NSCLC)患者XPD Lys751Gln(A/C)和XPD Asp312Asn(G/A)多态性与以铂类药物为基础的联合化疗临床疗效的相关性,为临床提供循证参考。方法:计算机检索PubMed、Cochrane图书馆、EMBase、Medline、中国期刊全文数据库、中文科技期刊数据库和万方数据库,收集有关NSCLC患者XPD Lys751Gln和XPD Asp312Asn多态性对以铂类药物为基础的联合化疗的有效性、临床结局和不良反应影响的研究,采用Rev Man 5.3统计软件进行Meta分析。结果:共纳入30项研究,合计5 028例患者。基因检测结果发现,XPD Lys751Gln分为变异型基因组(Lys/Gln+Gln/Gln)和野生型基因组(Lys/Lys),XPD Asp312Asn分为变异型基因组(Asp/Asn+Asn/Asn)和野生型基因组(Asp/Asp)。Meta分析结果显示,XPD Lys751Gln多态性中携带变异型基因组患者的无疾病进展生存期(PFS)明显低于携带野生型基因组的患者[MD=-1.12,95%CI(-1.73,-0.50),P<0.001],而化疗有效性(TR)和总生存期(OS)比较差异无统计学意义。XPD Asp312Asn多态性中携带变异型基因组患者的TR显著低于携带野生型基因组的患者[OR=0.80,95%CI(0.68,0.96),P=0.02],而PFS和OS比较差异均无统计学意义。安全性方面,XPD Lys751Gln多态性中携带变异型基因组患者的Ⅲ~Ⅳ级胃肠道不良反应发生率显著高于携带野生型基因组的患者[OR=0.43,95%CI(0.20,0.94),P=0.03),而Ⅲ~Ⅳ级血液系统不良反应发生率比较差异无统计学意义。结论:XPD Lys751Gln多态性与晚期NSCLC患者以铂类药物为基础的化疗的PFS和Ⅲ~Ⅳ级胃肠道不良反应有关,而XPD Asp312Asn多态性与以铂类药物为基础的化疗的有效性有关,两个位点均可作为预测NSCLC患者采用以铂类药物为基础的化疗治疗效果的考察靶点。
ABSTRACT: OBJECTIVE: To systematically review the relationship of clinical efficacy between XPD Lys751Gln (A/C), XPD Asp312Asn (G/A) and platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), and provide evidence-based reference for clinical treatment. METHODS: Retrieved from PubMed, Cochrane Library, EMBase, Medline, CJFD,VIP database and WanFang database, studies about the effects of XPD Lys751Gln and XPD Asp312Asn polymorphism on effectiveness, clinical outcomes and adverse drug reaction of platinum-based chemotherapy in advanced NSCLC patients were collected, and Meta-analysis was performed by using Rev Man 5.3 software. RESULTS: Totally 30 studies were included, involving 5 028 patients. Genetic testing showed that XPD Lys751Gln divided into mutant gene (Lys/Gln + Gln / Gln) and wild-type gene (Lys/Lys), while XPD Asp312Asn divided into mutant gene (Asp /Asn + Asn/Asn) and wild-type gene (Asp/Asp).  Results of Meta-analysis showed, the progression-free survival (PFS) of Lys/Gln+Gln/Gln patients with platinum in XPD Lys751Gln polymorphism was obviously lower than Lys/Lys patients [OR=-1.12,95%CI(-1.73,-0.50),P<0.001], while there was no significant difference in the chemotherapy effectiveness and total survival period. The effective rate of Asp/Asn+Asn/Asn patients for platinum in XPD Asp312Asn polymorphism was lower than Asp/Asp patients [OR=0.80, 95%CI(0.68, 0.96),P=0.02], while there was no significant difference in the total survival period and PFS. Meanwhile, the incidence of Ⅲ-Ⅳ level gastrointestinal adverse reactions of Lys/Gln+Gln/Gln with platinum in XPD Lys751Gln polymorphism was higher than Lys/Lys patients [OR=0.43, 95%CI(0.20,0.94),P=0.03], and there was no significant difference in Ⅲ-Ⅳ level blood system adverse reactions. CONCLUSIONS: XPD Lys751Gln polymorphism may be associated with PFS and Ⅲ-Ⅳ level gastrointestinal adverse reactions for advanced NSCLC patients with platinum-based chemotherapy, while XPD Asp312Asn polymorphism may have effect on platinum-based chemotherapy, both of them may be as estimate the chemotherapy effect and prognosis detection index of platinum-based chemotherapy.
期刊: 2016年第27卷第24期
作者: 滕雪,关尚为,刘朦朦,刘铎,董梅
AUTHORS: TENG Xue,GUAN Shangwei,LIU Mengmeng,LIU Duo,DONG Mei
关键字: XPD基因多态性;晚期非小细胞肺癌;铂类药物;临床疗效
KEYWORDS: XPD gene polymorphism; Advanced non-sm- all cell lung cancer; Platinum; Clinical efficacy
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