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

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)XPD751Lys/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)XPD751Lys/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,XPD751Lys/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。

Objective To investigate the relationship between the polymorphisms of DNA repair gene XPD751and the sensitivity to chemotherapy in advanced colorectal cancer.Methods A total of 98patients 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 XPD751Lys/Lys,Lys/Gln,Gln/Gln genetypes were 50.00%,29.41% and 20%,respectively,which was a significant difference（χ^2= 4.04,P〈0.05）.Logistic regression model results indicated that the probability of chemotherapy worked on patients with Lys/Lys genetype was 3.80fold 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.