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晚期非小细胞肺癌患者XPG基因多态性与铂类药物化疗敏感性的Meta分析

Correlation of XPG Gene Polymorphisms and Platinum based Chemotherapy Sensitivity in Patients with Advanced Non small Cell Lung Cancer: A Meta analysis

DOI：

中文关键词: XPG/ERCC5 基因多态性非小细胞肺癌铂类药物化疗敏感性

英文关键词:XPG/ERCC5 Polymorphism Advanced non small cell lung cancer Platinum Chemosensitivity

基金项目:黑龙江省卫生计生委科研课题项目（编号：2017 120），哈尔滨医科大学附属肿瘤医院海燕基金青年资助项目(编号:JJQN2014 04)

作者	单位
滕雪范晓凡邢玥董梅	哈尔滨医科大学附属肿瘤医院药学部哈尔滨150086

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中文摘要:

摘要目的：用Meta分析方法对晚期非小细胞肺癌（NSCLC）患者核苷酸切除修复基因XPG/ERCC5单核苷酸多态性与铂类药物化疗敏感性的相关性进行分析。方法：在PubMed、Cochrabe Libray、 Embase数据库和中国生物医学文献数据库（SinoMed）、中国学术期刊全文数据库（CNKI）、中文科技期刊全文数据库维普（VIP）、万方数据库中检索有关晚期NSCLC患者XPG/ERCC5基因46位点[XPG His46His]基因多态性与应用铂类药物化疗疗效相关性的研究，对符合标准的研究进行资料提取，采用Cochrane系统评价员手册5.1.0进行方法学质量评价，采用 RevMan 5.3软件进行Meta分析。结果：共纳入6项研究，合计983例患者。基因检测结果发现XPG His46His基因多态性分为变异型基因型C/T、T/T和野生型基因型C/C。Meta分析结果显示，晚期NSCLC患者携带XPG His46His基因中T/T基因型的化疗敏感性明显低于C/C基因型，差异有统计学意义（OR=0.40，95%CI：0.24~0.65，P=0.000 3）；而携带C/T基因型的化疗敏感性与C/C基因型比较差异无统计学意义（OR=0.80，95%CI：0.55~1.16，P=0.23）；携带变异型基因型C/T+T/T与野生型基因型C/C比较，携带变异型基因型的患者化疗敏感性低于野生型基因型C/C，差异有统计学意义（OR=0.56，95%CI：0.41~0.75，P=0.000 1）。另外亚组分析显示，病理分期为Ⅳ期的XPG His46His基因变异型与野生型相比，携带变异型C/T+T/T患者较野生型C/C对化疗敏感性降低，差异有统计学意义（OR=0.40，95%CI：0.20~0.82，P=0.01）。结论：晚期NSCLC核苷酸切除修复基因XPG/ERCC5野生型基因型C/C携带者对铂类化疗敏感性优于携带变异型基因型C/T+T/T、T/T的患者。但是由于纳入的研究数量较少，随着更多临床研究的开展，结论需要进一步验证。

英文摘要:

ABSTRACT Objective:Meta analysis was performed on the association between the nucleotide excision repair gene XPG/ERCC5 single nucleotide polymorphism and the sensitivity of platinum based chemotherapy in patients with advanced non small cell lung cancer. Methods:The advanced NSCLC patients with XPG His46His polymorphism and the efficacy of platinum based chemotherapy were retrieved via searching databases including PubMed, Embase, SinoMed, CNKI, VIP and WanFang database. Data were collected from standards compliant studies. Methodological quality evaluation was performed using the Cochrane System Evaluator Manual 5.1.0. Meta analysis was performed using RevMan 5.3 software. Results: The Meta analysis was conducted for 6 studies, involving 983 patients. Genetic testing showed that XPG His46His divided into mutant gene C/T, T/T and wild type gene C/C. Results of Meta analysis showed, TT type chemotherapy sensitivity in the XPG 46 locus genotype with advanced non small cell lung cancer patients was significantly lower than C/C genotype, the difference was statistically significant (OR=0.40, 95%CI: 0.24 0.65, P=0.000 3); there was no significant difference in sensitivity between C/T and C/C genotype (OR=0.80, 95%CI: 0.55 1.16, P=0.23]; the efficacy of type CT + TT genotype chemotherapy was significant lower than the wild type CC genotype, the difference was statistically significant (OR=0.56, 95%CI: 0.41 0.75, P=0.000 1). Subgroup analysis indicated that between C/T+T/T and C/C in the XPG 46 locus genotype, C/T+T/T type chemotherapy in the XPG 46 locus genotype sensitivity was significantly lower than CC genotype in pathological stage Ⅳ, the difference was statistically significant (OR=0.40, 95%CI: 0.20 0.82, P=0.01). Conclusion:Patients with advanced non small cell lung cancer nucleotide excision repair gene XPG / ERCC5 wild type C/C were more sensitive to platinum chemotherapy than those with variant genotype C/T + T/T and T/T. However, due to the small number of studies included in the systematic review, as more clinical studies were conducted, the conclusions need to be further verified.

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