XPD 751基因单核苷酸多态性与结肠癌术后mFOLFOX6化疗疗效及预后的关系

目的探讨DNA修复基因XPD 751位点单核苷酸多态性与结肠癌术后mFOLFOX6化疗疗效及预后的关系。 方法前瞻性选择2013年6月至2015年6月乐山市人民医院接受根治性手术的105例结肠癌患者作为结肠癌组，另选择同期100名健康者作为对照组。DNA测序技术检测XPD 751位点单核苷酸多态性以及基因型频率，mFOLFOX6方案化疗6个月后对患者进行疗效评价，Kaplan-Meier法和Cox多因素回归分析XPD 751位点基因位点多态性与预后的关系。 结果结肠癌组中XPD 751 AA基因型患者的疾病控制率（DCR）为86.44%（51/59），显著高于CA/CC基因型的65.22%（30/46）（χ²=6.603，P<0.05）。105例患者3年总生存率、无病生存率分别为69.52%、29.52%，其中AA基因型分别为77.97％、47.46%，高于CA/CC基因型的58.70%、6.52%，差异有统计学意义（χ²=4.712、20.817，P=0.030、<0.01），复发转移患者的AA基因型分布频率明显低于CA/CC基因型（30.51% vs 52.17%，χ²=5.055，P=0.025）。TNM分期和XPD 751 CA/CC基因型是影响结肠癌患者总体生存情况的危险因素（P=0.008、0.017）。 结论XPD 751位点CA/CC基因型结肠癌患者根治性术后mFOLFOX6化疗的敏感性差，无病生存率和总生存率较低，检测XPD 751位点基因多态性有助于评估结肠癌患者化疗疗效和预后。

Relationship between XPD 751 single nucleotide polymorphism and mFOLFOX6 chemotherapy efficacy and prognosis after colon cancer surgery

Objective To investigate the relationship between single nucleotide polymorphism of DNA repair gene XPD 751 and the efficacy and prognosis of mFOLFOX6 chemotherapy after colon cancer surgery.Methods From June 2013 to June 2015,one hundred and five patients with colon cancer who underwent radical operation in People’s Hospital of Leshan City were prospectively selected as colon cancer group and 100 healthy persons as control group.Single nucleotide polymorphism and genotype distribution at XPD 751 locus was detected by DNA sequencing.The efficacy was evaluated at 6 months after mFOLFOX6 chemotherapy.Kaplan-Meier method and multivariate Cox regression were used to analyze the relationship between the polymorphism of the XPD 751 locus and the prognosis of patients.Results The disease control rate(DCR)of patients with XPD 751 AA genotype in colon cancer group was 86.44%(51/59),significantly higher than 65.22%(30/46)of CA/CC genotype(χ^2=6.603,P<0.05).The 3-year overall survival rate and disease-free survival rate of the 105 patients were 69.52%and 29.52%respectively,and the AA genotype were 77.97%and 47.46%,higher than 58.70%and 6.52%of CA/CC genotype(χ^2=4.712,20.817,P=0.030,<0.01).The frequency of recurrence and metastasis in patients with AA genotype was significantly lower than that with CA/CC genotype(30.51%vs 52.17%,χ^2=5.055,P=0.025).TNM staging and XPD 751 CA/CC genotype were risk factors for overall survival in patients with colon cancer(P=0.008,0.017).Conclusions Colon cancer patients with XPD 751 CA/CC genotype show poor sensitivity to mFOLFOX6 chemotherapy,low disease-free survival rate and overall survival rate after radical operation.Detection of XPD 751 gene polymorphism is helpful to evaluate the efficacy and prognosis of chemotherapy in patients with colon cancer.