DNA修复基因XPD751单核苷酸多态性与 结直肠癌化疗疗效的相关性
Polymorphisms in XPD751 Gene and Sensitivity to Chemotherapy in Colorectal Carcinoma
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摘要: 目的 研究结直肠癌患者DNA修复基因XPD751单核苷酸多态性与铂类药物化疗敏感度的关系。方法 经病理学确诊的晚期结直肠癌患者98例，均行草酸铂联合5-氟尿嘧啶的方案（FOLFOX）治疗。所有病例化疗前抽取静脉血并提取DNA，采用多聚酶链反应-限制性片段长度多态性分析（PCR-RFLP）技术检测XPD751单核苷酸多态性。比较不同基因型与化疗疗效的关系。结果 （1）XPD751 Lys/Lys、Lys/Gln和Gln/Gln基因型频度分别为76（77.55%）、17（17.35%）和5（5.10%）。（2）XPD751 Lys/Lys、Lys/Gln 和Gln/Gln基因型有效率分别为50.00%、29.41%和20%，比较Lys/Lys、Lys/Gln的有效率，两者之间的差异有统计学意义（χ2=4.04，P<0.05）。在调整性别、年龄及不同转移部位的影响后，XPD751 Lys/Gln基因型患者化疗失败的可能性是Lys/Lys 基因型患者的3.8倍，OR=3.8，95%CI为0.985~14.698。结论 DNA修复基因XPD751单核苷酸多态性与结直肠癌对FOLFOX方案化疗敏感度相关，检测XPD751单核苷酸多态性可能成为预测结直肠癌患者接受FOLFOX方案化疗敏感度的指标。Abstract: Objective To investigate the relationship between the polymorphisms of DNA repair gene XPD751 and the sensitivity to chemotherapy in advanced colorectal cancer. Methods A total of 98 patients diagnosed as an advanced rectal cancer by the pathology were treated with FOLFOX chemotherapy and DNA of peripheral blood-leukocytes was obtained before the treatment，XPD genetype were detected by the PCR-RFLP method. Results （1）The frequencies of XPD751 Lys/Lys，Lys/Gln，Gln/Gln genetypes were 76 cases (77.55%)，17 cases (17.35%)，5 cases (5.10%) respectively.（2）The effective rate of FOLFOX chemotherapy among patients with XPD751 Lys/Lys，Lys/Gln，Gln/Gln genetypes were 50.00%，29.41% and 20%，respectively，which was a significant difference（χ2=4.04，P<0.05）.Logistic regression model results indicated that the probability of chemotherapy worked on patients with Lys/Lys genetype was 3.80 fold to Lys/Gln(OR=3.80，95%CI：0.985~14.698). Conclusion Single nucleotide polymorphisms of XPD751 correlates with the clinical response to FOLFOX chemotherapy and the XPD751 genetype detected by the PCR-RFLP method may be a predictor of sensitivity to FOLFOX chemotherapy.
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