XPD751基因多态性与晚期NSCLC对GP方案化疗的敏感性
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江苏省科技厅社会发展重点项目(No.BS2006005);江苏省卫生厅医学科研项目(No.Z200609)


Polymorphisms in XPD751 gene and sensitivity to Gemcitabine/Cisplatin chemotherapy in advanced stage of non-small-cell lung cancer
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    摘要:

    目的:研究DNA修复基因XPD751基因多态性与晚期非小细胞肺癌(NSCLC)对吉西他滨/顺铂(GP)方案化疗敏感性的关系。方法:收集经病理学确诊的晚期NSCLC 116例,所有病例化疗前抽静脉血,提取白细胞DNA,用多聚酶链反应—限制性片段长度多态性(PCR-RFLP)分析技术检测XPD751基因型,所有患者均为GP方案化疗。结果:① 在肺癌患者中,XPD751 Lys/Lys、Lys/Gln和Gln/Gln基因型分别为94例(81.0%)、20例(17.2%)和2例(1.8%)。经化疗后,44例患者有效,总有效率37.9%。②XPD751 Lys/Lys、Lys/Gln和Gln/Gln基因型有效率分别为39.4%、25.0%、100.0%,三者相比差异无统计学意义(χ2 = 4.775,P = 0.093) 。与携带Lys/Gln基因型患者相比,Lys/Lys基因型者对GP方案化疗效果无显著增加,调整性别、年龄、临床分期和细胞学类型后的OR=1.09,95%CI:0.95~1.51。③携带Lys/Lys基因型患者的恶心呕吐反应和脱发程度均高于Lys/Gln和Gln/Gln基因型患者(χ2 = 4.032,P = 0.045;χ2 = 4.344,P = 0.037)。结论:XPD751基因多态性与晚期NSCLC对GP方案化疗的敏感性无显著相关,但可作为预测GP方案化疗毒副反应的指标。

    Abstract:

    Objective:To investigate the relationship between polymorphisms of DNA repair gene XPD751 and sensitivity to Gemcitabine/Cisplatin(GP) chemotherapy in advanced non-small-cell lung cancer(NSCLC). Methods:116 patients with NSCLC were analyzed. All patients were treated with GP chemotherapy,and DNA of peripheral blood leukocytes was obtained before therapy. XPD751 genotypes were detected by PCR-RFLP method. Results:①Of all cases,the frequencies of XPD751 Lys/Lys,Lys/Gln and Gln/Gln genotype were 81.0%,17.2% and 1.8%,respectively. The overall response rate of chemotherapy in all patients was 37.9%. ② The response rate of chemotherapy among patients with XPD751 Lys/Lys,Lys/Gln and Gln/Gln genotypes were 39.4%,25.0%,100.0%,respectively,and no significant difference was found(χ2 = 4.775,P = 0.093). Comparing to patients with Lys/Gln genotypes,GP chemotherapy showed no significant superior effect in patients with Lys/Lys genotypes,adjusted for gender,age,clinical stage and cytology type(OR=1.09,95%CI:0.95~1.51)-③The incidence rate of vomiting/nausea and alopecie in Lys/Lys genotype was significantly higher than other genotypes(χ2 = 4.032,P = 0.045;χ2 = 4.344,P = 0.037). Conclusion:The polymorphisms of the XPD751 might not be associated with the clinical response to GP chemotherapy in advanced NSCLC,but could be used as a marker of toxicity prognosis.

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丁忠海,许 林,高长明,吴建中,史美祺,冯继锋.XPD751基因多态性与晚期NSCLC对GP方案化疗的敏感性[J].南京医科大学学报(自然科学版),2008,28(4):457-461

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