MDR1基因多态性与乳腺癌紫杉联合蒽环类药物化疗疗效的关系

王健

doi:10.3969/j.issn.1000-8179.2011.01.004

摘要: 目的：探讨多药耐药基因（MDR1）多态性对乳腺癌紫杉联合蒽环类（TA）化疗疗效的预测价值。方法：利用PCR-RFLP技术对142例乳腺癌患者进行MDR1基因变异检测，观察其多态性分布；并对其中接受TA方案的具有完整疗效评价资料的63例新辅助化疗患者，开展MDR1 12外显子C1236T、 21外显子G2677T/A和26外显子C3435T基因多态性与化疗疗效的相关分析。结果： C1236T、 G2677T/A和C3435T在142例中国汉族乳腺癌女性人群中的变异频率分别为70.7%、 55.0%和46.5%。其中， 3435TT基因型在63例新辅助化疗患者中表现出与TA疗效的关联，其有效率（23.1%）显著低于携带C等位基因的患者（73.5%； χ2=9.125， P=0.003）。3个位点多态之间存在连锁不均衡性，携带3435C-2677G单体型的患者，化疗有效率（72.1%）高于其他单体型携带者（40.0%； χ2=5.962， P=0.015），携带3435T-2677T或3435T-1236T单体型者，化疗有效率（54.3%或54.9%）低于对应的其他单体型携带者（82.4%和91.7%； χ2=4.128和χ2=4.118， P均为0.042）；携带有3435T-2677T-1236T单体型者，化疗有效率（54.3%）低于其他单体型携带者（82.4%； χ2=4.128， P=0.042）。结论： MDR1 C3435T基因型及其与G2677T/A和（或） C1236T的单体型检测对于乳腺癌TA联合化疗疗效的预测具有重要参考价值。

Abstract: Association Between MDR1 Gene Polymorphisms and Curative Effect ofTaxane-Anthracycline Chemotherapy in Breast CancerJian WANG1, Jinhai TAN2, Shanliang ZHONG3, Jianhua ZHAO3, Heqing SUN1, Fengxia ZHANG1, Jianping GONG1, MinghuaJI2Correspondence to: Jianhua ZHAO, E-mail: jhzhao2838@sina.com1Department of Breast Surgery, The First People's Hospital of Yangzhou City, Yangzhou 225000, China2Department of General Surgery, Jiangsu Tumor Hospital, Nanjing 210009, China3Center of Clinical Laboratory, Jiangsu Tumor Hospital, Nanjing 210009, ChinaThis work was supported by the grants from Social Development Project of Science Technology of Jiangsu Province (BS2007077)and the National Natural Science Foundation of China (30840093)Abstract Objective: To assess the predictive value of MDR1 gene polymorphisms for curative effect of combinationchemotherapy with taxane and anthracycline (TA). Methods: A total of 142 Chinese breast cancer patients were genotyped forMDR1 exon 12 C1236T, exon 21 G2677T/A and exon 26 C3435T using PCR-RFLP to observe the distribution of polymorphisms.The correlation between the MDR1 gene polymorphisms and effect of chemotherapy was analyzed in the 63 patients whoreceived neoadjuvant chemotherapy consisting of a TA regimen and had a complete follow-up. Results: The mutation frequenciesof exon 12 C1236T, exon 21 G2677T/A and exon 26 C3435T were 70.7%, 55.0% and 46.5%, respectively, in 142 female Hanpatients with breast cancer. In 63 of the patients who underwent the neoadjuvant chemotherapy, there was an associationbetween the 3435T genotype and decreased therapeutic response to the TA regimen, with an effective rate of 23.1%, significantlylower than the patients harboring the C allele ( 73.5%; χ2= 9.125, P = 0.003 ). The 3 single nucleotide polymorphism ( SNP )sites were in linkage disequilibrium. The efffect of chemotherapy was better in the patients with 3435C-2677G haplotype ( 72.1% )than in those with the other haplotypes ( 40.0%; χ2= 9.125, P = 0.003 ). The response rate to the chemotherapy was lower inthe patients with a 3435T-2677T or 3435T-1236T haplotype (54.3% or 54.9%) than in those harboring the other haplotypes (82.4% or 91.7%, χ2= 4.128 or χ2= 4.118, P = 0.042 ). The response rate was 54.3% in the patients with the 3435T-2677T-1236Thaplotype, much lower than the rate of 82.4% in those with the other haplotypes ( χ2= 4.128, P = 0.042 ). Conclusion: Ourfindings suggest that the MDR1 C3435T polymorphism and the accompanying C1236T and/or G2677T polymorphisms maybe of important reference value for predicting the effect of TA chemotherapy in breast cancer patients.Keywords MDR1; Polymorphisms; Breast cancer; Effect of chemotherapy