MDR1基因多态性与乳腺癌的相关性研究

Relationship between MDR1 gene polymorphism and breast carcinoma

目的探讨MDR1基因多态性与其在乳腺癌患者癌组织中表达水平、药物治疗反应及预后关系。方法选取153例乳腺癌组织及40例配对癌旁组织、20例乳腺纤维腺瘤组织,利用PCR-RFLP技术检测MDR1 exon12(1236)、exon21(2677)、exon26(3435)3个位点的多态性,以RT-q PCR技术对MDR1m RNA进行相对定量,分析不同基因型患者对药物治疗的反应及预后。结果 153例乳腺癌病例中有65例有MDR1基因扩增,总体扩增率为42.5%,表达值范围0~1.42×105基因拷贝/μl。在13例有效病例中,基因型CC型占11例、GT型占2例,而TT型则全部无效,TT型与其他型差异有统计学意义(P=0.031 7),其中C3435T的TT化疗疗效显著低于CC和GT型(P=0.006 5)。结论 MDR1基因在乳腺癌组织中的高表达,其SNP位点基因型可作为药物治疗反应及预后的预测因子。

Objective To investigate the relationship between MDR1 gene polymorphism, response to drug treatment and prognosis of breast carcinoma patients. Methods A total of 153 cases of breast cancer tissues, 40 cases matched adjacent tissues, and 20 cases of breast fibroadenoma tissue were studied.PCR-RFLP technique was used to detect MDR1 exon12(1236), exon21(2677), exon26(3435), 3 single nucleotide polymorphic(SNP) loci. RT-q PCR technique was used to detect relative expression level of MDR1 m RNA. Based on the results, response to drug treatment and prognosis of different genotypes were compared. Results Among the 153 cases of breast cancer, MDR1 gene amplification was successful in 65 cases, with an overall amplification rate of 42.5%. Expression values ranged from 0 to1.42×105gene copies/μl. Among the 13 cases of effective cases, genotype CC accounted for 11 cases,GT accounted for 2 cases. Genotype TT were all invalid. There is a significant difference between the TT and other types(P=0.031 7). The chemotherapy effectiveness in the C3 435 T type is significantly lower than those in the CC and GT type(P=0.006 5). Conclusions The expression level of MDR1 gene in breast cancer, and the gene polymorphism can be predictors of drug response and prognosis in chemotherapy treatment.