乳腺癌MDR1基因多态性与其表达及化疗血液毒性的关系  

Relations of MDR-1 polymorphism in breast cancer with its gene expression and chemotherapy-induced hematologic toxicity

作　　者：刘学敏[1,2] 王树生[1] 

机构地区：[1]南京中医药大学附属张家港市中医院普通外科,江苏张家港215600 [2]南京医科大学附属肿瘤医院普通外科,江苏南京210009

出　　处：《中国普通外科杂志》2012年第11期1394-1397,共4页China Journal of General Surgery

摘　　要：目的:探讨乳腺癌多药耐药基因MDR1基因多态性与其表达及与化疗血液毒性之间的关系。方法:提取92例乳腺癌患者外周静脉血DNA,利用限制性片段长度多态性(PCR-RFLP)技术检测MDR1外显子(exon)26(C3435T)位点的多态性,并用RT-qPCR方法检测该92例患者癌组织及其中26例配对癌旁组织MDR1 mRNA的表达。根据患者的临床资料,分析C3435T位点多态性与化疗血液学毒性的关系。结果:92例乳腺癌中,C3435T位点CC,CT,TT 3种基因型分别占21.7%(20/92),62.0%(57/92)和16.3%(15/92),所有乳癌组织中均有不同程度的MDR1 mRNA表达,但各基因型间MDR1 mRNA表达水平差异无统计学意义(F=0.173,P=0.841);癌组织MDR1 mRNA表达水平明显高于其对应的癌旁组织[(3.83±5.27)vs.(1.81±4.42),t=2.522,P=0.018]。C3435T各基因型患者中性粒细胞减少反应差异有统计学意义,CC型中性粒细胞减少(III～IV度)的发生频率(5.0%)明显低于CT和TT型(26.3%和46.7%;χ2=8.075,P=0.018,95%CI=0.017～0.022),而白细胞减少、贫血、血小板减少等方面各基因型间无统计学差异(均P>0.05)。结论:乳腺癌患者MDR1基因C3435T位点多态性与MDR1基因表达水平无明显关系,CT和TT型患者化疗后发生中性粒细胞减少症的风险较大。Objective： To investigate the relations of multidrug resistance gene MDR1 polymorphism in breast cancer with its gene expression and chemotherapy-induced hematologic toxicity. Methods： Genomic DNA was extracted from peripheral venous blood samples from 92 patients with breast cancer, and the polymorphism of MDR1 exon 26 （C3435T） was analyzed by PCR-restriction fragment length polymorphism （PCR-RFLP） technique. The MDR1 mRNA expressions in the breast cancer tissues from these 92 patients and the adjacent tissues from 26 of these cases were determined by RT-qPCR method. Furthermore, the relation of C3435T potymorphism with chemotherapy-induced hematologic toxicity was analyzed according to the clinical data of the patients. Results： In the 92 breast cancer patients, the three C3435T genotypes, CC, CT and qT accounted for 21.7% （20/92）, 62.0% （57/92） and 16.3% （15/92）, respectively. M1 the breast cancer tissues showed MDR1 mRNA expression of different levels, but the differences among the genotypes had no statistical significance （F=0.173, P=0.841）. The expression level of MDR1 mRNA in breast cancer tissues was significantly higher than that in their paired adjacent tissues （3.83±5.27 vs. 1.81±4.42, t=2.522, P=0.018）. There was statistical difference in incidence of neutropenia among patients with different C3435T genotypes, in which, the incidence of neutropenia （grade Ⅲ-Ⅳ） in patients with CC genotype （5.0%） was significantly lower than that in patients with CT or TT genotype （26.3% and 46.7%; X^2=8.075, P=0.018, 95%CI=0.017-0.022）. There was no significant difference in the incidences ofleucopenia, anemia and thrombocytopenia among genotypes （all p〉0.05）. Conclusion： MDR1 C3435T polymorphism is irrelevant to MDR1 gene expression in patients with breast cancer, and the patients with TT or CT genotype may have an increased risk of developing chemotherapyinduced neutropenia.

关 键 词：乳腺肿瘤 P糖蛋白 多态性 单核苷酸 药物毒性 

分 类 号：R737.9[医药卫生—肿瘤]