化疗药物代谢酶相关基因SNPs分析及其在肿瘤个体化治疗中的探讨

SNPs analysis of chemotherapeuic drug-metabolizing enzyme associated gene and discussion in tumor individual therapy

目的建立化疗药物代谢酶相关基因SNPs位点分析方法,探讨其在肿瘤个体化治疗中的可行性。方法自行设计PCR引物扩增化疗药物代谢酶相关基因DPYD、GSTP1、MTHFR和XRCC1相关片段,建立基于基因测序的SNPs分析方法,并用于临床4例肿瘤患者、2例健康对照样品分析。结果成功建立了化疗药物代谢酶相关基因SNPs位点分析方法。6例样品共得到24个测序结果,其中1例肿瘤患者GSTP1基因为突变型,预测其化疗疗效较好,可减少药物剂量。结论药物代谢酶相关基因DNA测序能为临床制订个体化治疗方案提供依据,指导医生选择合适并适量的化疗药物。

Objective To establish a method of determining SNPs of chemotherapeuic drug-metabolizing enzyme associated gene. Discuss the feasibility of this SNPs analysis method in individual therapy for tumor patients. Methods The target gene fragments of chemotherapeuic drug-metabolizing enzyme associated gene,including DPYD, GSTP1, MTHFR and XRCC1, were amplificared by PCR and analyzed by gene sequencing. Results SNPs analysis method for chemotherapeuic drug-metabolizing enzyme associated gene was succesfully established. Among the 24 sequncing results of 6 clinical samples, A GSTP1 gene from a tumour patient was mutant. It suggested that this tumour patient will have a better chemotherapy effect and could have a less dosage. Conclusion It is feasibility to take our established PCR-amplification-DNA-sequencing method for analyzing SNPs of chemotherapeuic drug-metabolizing enzyme associated gene. The analysis results could guide doctors to selected chemotherapyeutic drugs and dose for clinical individual patient.