DNA修复基因XPD751单核苷酸多态性与结直肠癌预后的关系

Relationship between single nucleotide polymorphism in repair gene XPD751 and prognosis in colorectal carcinoma patients

目的 探讨结直肠癌患者DNA修复基因XPD751单核苷酸多态性与铂类药物化疗疗效的关系。方法经病理学确诊的晚期结直肠癌患者98例，均行奥沙利铂联合氟尿嘧啶化疗方案（FOLFOX）治疗。所有患者化疗前抽取静脉血，成功提取DNA，采用多聚酶链反应-限制性片段长度多态性分析技术检测XPD751单核苷酸多态性。比较不同基因型与预后的关系。结果98例结直肠癌患者中，DNA修复基因XPD751各基因型频度分别为Lys／Lys基因型占77．6％（76／98），Lys／Gln基因型占17．4％（17／98），Gin／Gin基因型占5．1％（5／98）。98例结直肠癌患者部分缓解44例（44．9％），疾病稳定34例（34．7％），疾病进展20例（20．4％）。携带XPD751Lys／Lys基因型的患者化疗的有效率为50．0％，Lys／Gln基因型为29．4％，Gln／Gln基因型为20．0％。携带Lys／Lys基因型患者的化疗疗效优于携带Lys／Gln基因型的患者，差异有统计学意义（P〈0．05）。Logistic回归分析显示，携带Lys／Lys基因型的患者接受FOLFOX方案化疗的敏感性是携带Lys／Gln基因型患者的3．800倍（OR=3．800，P=0．016）。98例结直肠癌患者的疾病进展时间（TTP）为10．1个月，携带XPD751Lys／Lys基因型患者的中位1TrP为11．3个月，携带Lys／Gln和Gln／Gln基因型患者的中位TTP为2．9个月。携带bs／Lys与至少有1个Gin基因型患者的中位1rrP比较，差异有统计学意义（P〈0．05）。Cox回归分析显示，携带Lys／Gln基因型的患者疾病进展的风险是携带Lys／Lys基因型患者的2．035倍（RR=2．035，P=0．001）。结论DNA修复基因XPD751单核苷酸多态性可能与结直肠癌患者对FOLFOX方案化疗敏感性有关，检测XPD751单核苷酸多态性可能成为预测接受FOLFOX方案化疗后结直肠癌患者预后的指标。

Objective To investigate whether single nucleotide polymorphism （SNP） in DNA repair gene XPD751 is associated with sensitivity and time to progression （TFP） for platinum-containing combination chemotherapy in advanced colorectal carcinoma. Methods A total of 98 patients pathologically diagnosed as advanced colorectal cancer were treated with FOLFOX chemotherapy. TheDNA of peripheral blood-leukocytes was obtained before treatment, and XPD genetype was detected by PCR-RFLP analysis. Results The frequency of XPD751 Lys/lys was 76 cases （77.6%）, lys/Gln 17 cases （ 17.4% ）, and Gin/Gin genetype 5 cases （ 5. 1% ）. The effective rate of FOLFOX chemotherapy among patients with XPD751 Lys/lys was 50.0%, lys/Gln 29.4% , and Gln/Gln genetypes 20.0%. The difference between Lys/lys and lys/Gln was statistically significant, X2 = 4.04, P 〈 0.05. The results indicated that the failure of chemotherapy in patients with Lys/Lys genetype was 3. 8-fold to those with Lys/Gln, by adjusting of gender, age, and tumor metastasis （ OR = 3. 800）. The MTFP of the 98 patients was 10. 1 months. The MTFP was 11.3 months for patients with Lys/Lys genotypes of XPD751 gene and 2.9 months for patients with Lys/Gln and Gln/Gln genotypes of XPD751 gene, the difference between Lys/Lys and at least one Gin was significant （ P 〈 0.05 ）. Conclusions Single nucleotlde polymorphism of XPD751 correlates with the clinical response to FOLFOX chemotherapy. XPD751 genetic polymorphisms may be associated with TFP of advanced colorectal carcinoma patients treated with oxaliplatin as the first line chemotherapy. XPD751 genotype detected by the PCR-RFLP method may be a predictor of prognosis for FOLFOX chemotherapy.