MDR1 G2677T基因多态性在预测紫杉醇为主的化疗方案治疗晚期消化系难治性恶性肿瘤疗效中的价值

Value of MDR1 G2677T genetic polymorphism in predicting efficacy of aclitaxel-based chemotherapy in refractory advanced gastrointestinal malignancies

目的:探讨MDR1 G2677T基因多态性与紫杉醇为主的化疗方案治疗晚期消化系难治性恶性肿瘤疗效的关系.方法:97例晚期消化系难治性恶性肿瘤患者给予以紫杉醇为主的化疗方案(130 mg/m^2,静脉滴注,d1、8,21 d为1周期),评价疗效,于治疗前抽取患者外周血提取DNA,采用PCR扩增目的基因片段,直接测序法测定MDR1G2677T基因多态性,分析MDR1 G2677T基因多态性与疗效关系.结果:最终有94例患者完成了本研究,其中完全缓解(complete response,CR):2例,部分缓解(partial response,PR):24例,疾病稳定(stable disease,SD):54例,疾病进展(progressive disease,PD):14例,总缓解率为27.66%.MDR1 G2677T基因野生型G/G有32例,突变型中有62例(A/A有6例,T/T有14例,G/A有10例,G/T有12例,A/T有20例),两类基因型与肿瘤发生部位无明显相关性.MDR1G2677T基因多态性与疗效相关(P<0.05),其中仅MDR1 G2677T野生型G/G对疗效的影响有统计学意义(P<0.01).结论:MDR1 G2677T基因多态性可作为遗传学标志预测紫杉醇对晚期消化系难治性恶性肿瘤患者的化疗敏感性,野生型G/G基因携带者化疗疗效优于其他基因型携带者.

AIM：To investigate the correlation of the MDR1G2677 T genetic polymorphism with effi cacy of paclitaxel-based chemotherapy in patients with refractory advanced gastrointestinal malignancies.METHODS：Ninety-seven patients with refractory advanced gastrointestinal malignancies received paclitaxel-based chemotherapy（130 mg/m^2,d1,8,every 3 wk）.Efficacy was evaluated after treatment.The MDR1 G2677 T genetic polymorphism was detected by amplifying the gene fragments using PCR and direct sequencing.The correlation of the MDR1 G2677 T genetic polymorphism with effi cacy was then analyzed.RESULTS：Totally 94 patients completed the study.Two cases had complete response,24 cases had partial response,54 cases had stable disease,and 14 cases had progression disease.The overall response rate was 27.66%.The MDR1 G2677 T wild-type genotype G/G was detected 32 cases,and mutant genotypes were detected in 62 cases（A/A,6 cases;T/T,14 cases;G/A,10 cases;G/T,12 cases;A/T,20 cases）.There was no signifi cant correlation between tumor location and genotypes.There was a significant correlation between MDR1G2677 T genetic polymorphism and effi cacy（P 〈0.05）.A signifi cant correlation was observed only between the MDR1 G2677 T wild-type genotype G/G and chemotherapeutic effects（P 〈0.01）.CONCLUSION：The MDR1 G2677 T genetic polymorphism can be used to predict response to paclitaxel-based chemotherapy in patients with refractory advanced gastrointestinal malignancies.The MDR1 G2677 T wild-type genotype G/G may be associated with a better treatment response compared with other genotypes.