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目的:探讨细胞色素P450(CYP)3A4基因多态性与晚期胃癌患者紫杉醇化疗敏感性的相关性。方法:选择昆明医科大学第三附属医院2014年3-9月确诊为晚期胃癌的患者67例,于化疗前静脉采血,采用聚合酶链反应-限制性片段长度多态性分析法检测其CYP3A4基因多态性。所有患者均予以紫杉醇为基础的两药联合化疗方案,按实体瘤疗效评价标准评价疗效,以客观缓解率(ORR)评价化疗敏感性,并分析患者不同基因型与化疗敏感性的相关性。结果:67例晚期胃癌患者的ORR为38.8%;CYP3A4*2(+)、CYP3A4*3(+)、CYP3A4*4(+)基因型患者分别占23.9%、28.4%、26.9%;CYP3A4*3(+)与CPY3A4*3(-)基因型患者的ORR分别为57.9%、31.3%,差异有统计学意义(P=0.044),该基因型与化疗敏感性相关[比值比(OR)=3.731,95%置信区间(CI)(0.901,15.897)];CYP3A4*2(+)与CYP3A4*2(-)基因型患者的ORR分别为43.7%、37.3%,差异无统计学意义(P=0.642),该基因型与化疗敏感性不相关[OR=1.075,95%CI(0.274,16.289)];CYP3A4*4(+)与CYP3A4*4(-)基因型患者的ORR分别为33.3%、40.8%,差异无统计学意义(P=0.577),该基因型与化疗敏感性不相关[OR=0.938,95%CI(0.735,14.732)]。结论:CYP3A4*3基因多态性有可能成为预测晚期胃癌患者紫杉醇类药物化疗敏感性的分子标志物。
OBJECTIVE: To explore the association between CYP3A4 gene polymorphism and the sensitivity of advanced gastric cancer patients to paclitaxel chemotherapy. METHODS: 67 patients diagnosed as advanced gastric cancer were selected from the Third Affiliated Hospital of Kunming Medical University during Mar.-Sep. 2014. Blood samples were collected before chemotherapy, and PCR-RFLP analysis was performed to detect CYP3A4 gene polymorphism. All patients were given two-drug chemotherapy based on paclitaxel. Therapeutic efficacy was evaluated by solid tumor therapeutic efficacy evaluation criteria, and objective remission rate (ORR) was used to evaluate chemotherapy sensitivity; the association between different genotypes and chemotherapy sensitivity was analysed. RESULTS: ORR of 67 patients with advanced gastric cancer was 38.8%; CYP3A4*2(+), CYP3A4*3(+), and CYP3A4*4(+) genotype patients accounted for 23.9%, 28.4%, and 26.9% respectively. ORR of patients with CYP3A4*3(+)and CPY3A4*3(-)genotype were 57.9% and 31.3%, with statistical significance (P=0.044); this genotype was associated with chemotherapy sensitivity [OR=3.731, 95%CI(0.901,15.897)]. ORR of patients with CYP3A4*2(+)and CYP3A4*2(-)genotype were 43.7% and 37.3%, without statistical significance (P=0.642); this genotype was not associated with chemotherapy sensitivity [OR=1.075, 95%CI(0.274,16.289)]. ORR of patients with CYP3A4*4(+)and CYP3A4*4(-)were 33.3% and 40.8%, without statistical significance (P=0.577); this genotype was not associated with chemotherapy sensitivity [OR=0.938, 95%CI(0.735,14.732)]. CONCLUSIONS: CYP3A4*3 gene polymorphism may become a biomarker for predicting the sensitivity in advance gastric cancer patients to paclitaxel chemotherapy.
CYP3A4基因多态性紫杉醇晚期胃癌化疗敏感性相关性
CYP3A4 gene polymerphismsPaclitaxelAdvance gastric cancerChemotherapy sensitivityAssociation
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