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目的探讨DNA修复基因XPD751和XPD312单核苷酸多态性与FOLFOX方案治疗中国晚期结直肠癌患者疗效的相关性;探讨两种基因单核苷酸多态性在晚期结直肠癌患者预后评估中的预测价值。方法收集2008-01-01-2013-12-31我院经病理学确诊并接受FOLFOX方案治疗的晚期结直肠癌76例患者,采集患者化疗前外周静脉血,经DNA提取后采用限制性片段长度多态性聚合酶链反应(RFLP-PCR)技术检测XPD751和XPD312的单核苷酸多态性,比较不同基因型与化疗疗效及预后的相关性。结果 XPD751野生型和突变型的分布频度分别为76.3%和23.7%,XPD312野生型和突变型的分布频度分别为55.3%和44.7%;XPD751野生型组和突变型组的疾病控制率(DCR)分别为79.3%和77.7%,XPD312分别为64.2%和79.4%,XPD751野生型患者化疗有效率优于突变型患者,χ2=5.141,P=0.007;Logistic回归分析显示,携带XPD751野生型患者接受FOLFOX方案化疗的敏感性是携带突变型患者的3.5倍,OR=3.500,P=0.015。XPD312野生型组和突变型组化疗疗效差异无统计学意义,χ2=2.456,P=0.483。XPD751野生型和突变型的中位无进展生存期(PFS)分别为9.96和7.8个月,XPD312分别为9.88和8.41个月。XPD751两类基因型的中位PFS差异有统计学意义,χ2=11.769,P=0.001;XPD312两类基因型的中位PFS差异无统计学意义,χ2=1.479,P>0.05。同时携带XPD751野生型和XPD312野生型的PFS为12.95个月,同时携带XPD751野生型和XPD312突变型的PFS为8.36个月,同时携带XPD751突变型和XPD312野生型的PFS为7.8个月,同时携带XPD751突变型和XPD312突变型的PFS为7.14个月,组间差异有统计学意义,χ2=12.722,P=0.005。Cox回归分析性别、年龄、肿瘤转移部位及上述四类基因分型与PFS的相关性显示,只有基因分型与PFS相关,P<0.001,RR=1.445;分析上述四类基因分型,只有同时携带XPD751野生型和XPD312野生型的基因分型与PFS相关,P=0.006,RR=0.357。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方案化疗敏感性相关,检测XPD751单核苷酸多态性可能成为预测FOLFOX方案化疗敏感性和晚期结直肠癌患者预后的指标。XPD751和XPD312均为野生型患者可能对FOLFOX化疗更加敏感,预后更好。XPD312单核苷酸多态性可能与晚期结直肠癌患者对FOLFOX方案化疗敏感性及预后无相关性。
Objective To investigate the association between single nucleotide polymorphisms of DNA repair gene XPD751 and XPD312 and the efficacy of FOLFOX regimen in the treatment of patients with advanced colorectal cancer in China. To investigate the prognosis of patients with advanced colorectal cancer by two single nucleotide polymorphisms The predictive value. Methods A total of 76 patients with advanced colorectal cancer diagnosed by pathology and receiving FOLFOX regimen in our hospital from January 1, 2008 to January 2008 were enrolled in this study. Peripheral venous blood samples were collected before DNA extraction. The restriction fragment length Single nucleotide polymorphisms (SNPs) of XPD751 and XPD312 were detected by RFLP-PCR, and the correlation between different genotypes and chemotherapy outcomes and prognosis was compared. Results The distribution frequencies of wild type and mutant type of XPD751 were 76.3% and 23.7% respectively, and the distribution frequency of wild type and mutant type of XPD312 were 55.3% and 44.7% respectively. The disease control rate of wild type and mutant type of XPD751 DCR) were 79.3% and 77.7%, XPD312 was 64.2% and 79.4%, XPD751 wild-type patients with chemotherapy better than mutant patients, χ2 = 5.141, P = 0.007; Logistic regression analysis showed that XPD751 wild-type patients The sensitivity of chemotherapy with FOLFOX regimen was 3.5 times that of patients with mutation, OR = 3.500, P = 0.015. There was no significant difference in the efficacy of XPD312 wild-type and mutant chemotherapy (χ2 = 2.456, P = 0.483). The median progression-free survival (PFS) of XPD751 wild-type and mutant were 9.96 and 7.8 months, respectively, and XPD312 was 9.88 and 8.41 months, respectively. The median PFS of XPD751 genotypes was statistically significant (χ2 = 11.769, P = 0.001). There was no significant difference in median PFS between XPD312 genotypes (χ2 = 1.479, P> 0.05). The mean PFS carrying both XPD751 wild-type and XPD312 wild-type was 12.95 months, PFS carrying both XPD751 wild-type and XPD312 mutant was 8.36 months, PFS carrying both XPD751 mutant and XPD312 wild-type was 7.8 months, The PFS of XPD751 mutant and XPD312 mutant was 7.14 months. The difference between the two groups was statistically significant (χ2 = 12.722, P = 0.005). Cox regression analysis of gender, age, location of tumor metastasis and the above four types of genotyping and PFS showed that only genotyping and PFS, P <0.001, RR = 1.445; analysis of the above four types of genotyping, only at the same time Genotypes carrying XPD751 wild-type and XPD312 wild-type were associated with PFS, P = 0.006, RR = 0.357. Conclusion Single nucleotide polymorphism of DNA repair gene XPD751 may be associated with chemosensitivity to FOLFOX regimen in patients with colorectal cancer. Detecting XPD751 single nucleotide polymorphisms may be predictors of chemosensitivity to FOLFOX regimen and prognosis of patients with advanced colorectal cancer index of. Patients with both wild-type XPD751 and XPD312 may be more sensitive to FOLFOX chemotherapy and have a better prognosis. XPD312 SNP may not be associated with chemosensitivity and prognosis of FOLFOX regimen in patients with advanced colorectal cancer.