ABCB1基因多态性对乳腺癌紫杉类药物化疗疗效的影响
Influence of ABCB1 gene polymorphisms on breast cancer with paclitaxel-based chemotherapy

摘要：目的 检测乳腺癌患者多药耐药(ABCB1/MDR1)基因多态性，分析其与乳腺癌患者应用紫杉类药物化疗疗效的关系。方法 采用PCR-HRM技术检测146例Ⅳ期乳腺癌患者ABCB1exon12(C1236T)、exon21(G2677T/A)和exon26(C3435T)基因分型，探讨其与乳腺癌患者应用紫杉类药物化疗疗效的关系。结果 146例Ⅳ期乳腺癌患者中，C1236T位点CC基因型占15.86%，CT基因型占44.83%，TT基因型占39.31%；G2677T/A位点GG基因型占16.67%，GT基因型占45.83%，GA基因型占6.25%，TT基因型占28.47%，AT基因型占2.78%；C3435T位点CC基因型占22.22%，CT基因型占56.25%，TT基因型占21.53%。回族与汉族病例组中ABCB1待测位点基因多态性相比，差异无统计学意义(P>0.05)。经Hardy-Weinberg遗传平衡检验，认为C1236T、G2677T/A和C3435T基因多态性具有群体代表性(P>0.05)。146例Ⅳ期乳腺癌患者接受以紫杉为基础的化疗方案，C3435T位点CT/TT基因型患者有74.11%较好的反应率(χ2=12.556，P<0.05)，化疗疗效优于CC基因型(OR=4.183，95% CI 1.838～9.521，P<0.05)，T等位基因携带者化疗有效率高于C等位基因携带者(χ2= 8.507， P<0.05)。结论 检测ABCB1基因C3435T位点基因多态性对预测乳腺癌患者应用紫杉类药物化疗疗效有重要的临床参考价值。
ABSTRACT: Objective To detect gene polymorphisms of ABCB1/ MDR1 in breast cancer and to analyze the association between ABCB1 gene polymorphisms and curative effect of paclitaxel-based chemotherapy in breast cancer. Methods Genotyping of ABCB1exon12 (1236), exon21 (2677) and exon26 (3435) was determined by polymerase chain reaction (PCR)-high resolution melting (HRM) method in 146 cases of female stage IV breast cancer to explore the relationship between the efficacy of chemotherapy in breast cancer patients with paclitaxel chemotherapy. Results In 146 patients with stage IV breast cancer, C1236T CC genotype accounted for 15.86%, CT genotype 44.83%, TT genotype 44.83%, G2677T/A GG genotype 16.67%, GT genotype 45.83%, GA genotype 6.25%, TT genotype 28.47%, AT genotype 2.78%, C3435 CC genotype 22.22%, CT genotype 56.25%, and TT genotype 21.53%. ABCB1 gene polymorphisms did not significantly differ between patients of Hui and Han Nationalities (P>0.05). Hardy-Weinberg genetic equilibrium testing showed that polymorphisms of C1236T, G2677T/A and C3435T had group representation (P>0.05). In 146 stage IV breast cancer patients who had received paclitaxel-based chemotherapy, CT/TT genotype of C3435T site had a better response rate (74.11%)(χ2=12.556, P<0.05), better curative effect than CC genotype (OR=4.183, 95% CI 1.838-9.521, P<0.05), T allele carriers more efficient than C allele carriers with paclitaxel-based chemotherapy (χ2=8.507, P<0.05). Conclusion Detection of ABCB1 C3435T gene polymorphisms has a significantly clinical value in predicting the efficacy of taxanes chemotherapy in breast cancer patients