结直肠癌基因XPD751和XPD312单核苷酸多态性与FOLFOX方案疗效相关性分析  

Relationship between single nucleotide polymorphisms in repair gene XPD751,XPD312 and prognosis in colorectal carcinoma patients

作　　者：陈雅敏[1] 刘基巍[1] 张昉[1] 

机构地区：[1]大连医科大学附属第一医院肿瘤一科,辽宁大连116000

出　　处：《中华肿瘤防治杂志》2014年第24期1946-1951,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：2011年辽宁省科技厅计划(2011225013)

摘　　要：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OBJECTIVE To investigate whether single nucleotide polymorphisms （SNP） in XPD751 and XPD312 of DNA repair gene are associated with the sensitivity of FOLOFX regimen in advanced colorectal carcinoma. To investigate whether SNPs in XPD751 and XPD312 of DNA repair gene can predict progression-free survival （PFS） in advanced colorectal carcinoma. METHODS A total of 76 patients diagnosed as advanced colorectal cancer by experienced pathologist from 2008-01-01 to 2013-12-31 in our hospital were treated with FOLFOX regimen. The DNA of peripheral blood-leukocytes was obtained before treatment, and the SNPs in XPD751 and XPD312 of DNA repair gene were detected by RFLP-PCR analysis. RESULTS The frequencies of wild type and mutant of XPD751 were 76.3% and 23.7% respectively. The frequencies of wild type and mutant of XPD312 were 55.3% and 44.7% respectively. The disease control rates （DCR） of patients with wild type and mutant of XPD751 were 79. 3% and 77. 7% respectively. The DCR of patients with wild type and mutant of XPD Asp312 were 64.2 % and 79.4% respectively. The difference of DCR between wild type and mutant of XPD751 was statistically significant （Х^2 = 5. 141, P= 0. 007）. The Logistic Regression Analysis indicated that the chemotherapy sensitivity in patients with wild type XPD751 was 3.5 times higher than that with mutant XPD751. There was no significant difference between wild type and mutant of XPD312 when the DCR was concerned （Х^2 = 2. 456, P= 0. 483）. The median progression free survival （MPFS） of patients harbored wild type and mutant XPD751 was 9.96 and 7.8 months respectively. The difference of MPFS between these two groups was significant （Х^2= 11. 769, P = 0. 001 ）. The MPFS of patients harbored wild type and mutant XPD312 was 9.88 and 8.41 months respectively. There was no significant difference of MPFS between these two groups （Х^2 = 1. 479, P〈0.05）. The MPFS was 12. 95 months for patients with both of wild type XPD751 and XPD312, 8.36 months for patients with bo

关 键 词：结直肠肿瘤 单核苷酸多态性 FOLFOX方案 XPD751 XPD312 

分 类 号：R735.34[医药卫生—肿瘤]