乳腺癌MDR1基因多态性与紫杉类药物化疗血液毒副反应的关系

Association between MDR1 polymorphisms and blood-related side effects in breast cancer patients with taxanes-based chemotherapy

目的:探讨MDR1基因多态性与乳腺癌紫杉类药物为基础化疗毒副反应间的关系,为临床个体化药物治疗提供信息。方法:筛选93例汉族女性乳腺癌患者,利用PCR-RFLP技术检测其外周血MDR1 C3435T和G2677T/A基因型。结果:在本组病例中,白细胞和中性粒细胞减少症(Ⅲ～Ⅳ度)的发生频率相对较高,分别为27.2%和25%。MDR1 C3435T各基因型患者间中性粒细胞减少反应差异显著,CC型发生频率为5%,低于CT和TT型(26.3%和46.7%;χ2=8.075,P=0.018;95%CI0.017～0.022);未发现G2677T/A多态性与血液毒性的关联。结论:MDR1 3435T等位基因携带者在紫杉类药物治疗后发生中性粒细胞减少症的风险可能较大。

Objective To investigate whether muhidrug resistance 1 （MDR1） gene polymorphisms are associated with the toxicity of taxanes-based chemotherapy in breast cancer patients. Methods Genotyping of MDR1 polymorphisms C3435T and G2677T variants were determined by PCR-RFLP technique in the blood samples from 93 Chinese Han patients with breast cancer. Results The incidence of leukopenia and neutropenia （grade m- IV） were 27.2% and 25% respectively. The patients carrying MDR1 3435CC showed a significantly lower toxicity response rate of neutropenia （5%） than those with 3435CT and 3435TY（26.3% and 46.7%; χ2= 8.075, P = 0.018; 95% CI： 0.017-0.022）. However, There was no relationship between G2677T/A polymorphisms and hematologic toxicities. Conclusions The patients carrying MDRI 3435T allele may have an increased risk of developing neutropenia for the toxicity of taxanes-based chemotherapy.