| 刘 磊,孔凡巍,李庆华.CYP19A1基因多态性与晚期乳腺癌阿那曲唑治疗疗效相关性研究[J].中国肿瘤,2017,26(9):740-744. |
| CYP19A1基因多态性与晚期乳腺癌阿那曲唑治疗疗效相关性研究 |
| Polymorphisms of CYP19A1 Gene Associated with the Efficacy of Anastrozole in Metastatic Breast Carcinoma |
| 投稿时间：2016-10-23 |
| DOI：10.11735/j.issn.1004-0242.2017.09.A015 |
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| 中文关键词: 乳腺癌 CYP19A1基因 阿那曲唑 预后 基因多态性 |
| 英文关键词:breast cancer CYP19A1 gene anastrozole prognosis gene polymorphism |
| 基金项目:黑龙江省教育厅科学技术研究项目（12541503） |
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| 中文摘要: |
| 摘 要：［目的］研究CYP19A1基因的rs4646和rs10046位点多态性与晚期乳腺癌阿那曲唑治疗疗效的相关性。［方法］ 本研究共纳入272例激素受体阳性晚期乳腺癌患者，接受阿那曲唑治疗后抽取患者外周静脉血，提取DNA，多重 PCR获取目的基因片段后，采用直接测序法分析CYP19A1基因多态性。对比等位基因分布频率在突变型和野生型两组患者中的差异。［结果］ 被检测的rs4646和rs10046符合Hardy-Weinberg平衡检验；比较rs4646突变型和野生型两组阿那曲唑疗效，32例完全缓解的患者中24例是rs4646突变型，76例疾病进展者中有60例是rs4646野生型，P<0.005，经过Bonferroni 矫正Ｐ值仍有统计学意义。与rs4646野生型相比，携带rs4646突变型患者的中位生存期（median survival time，MST）显著延长（Log-rank检验 P=0.007）。携带rs4646突变型患者的疾病进展时间（time to progression，TTP）显著延长（Log-rank检验 P=0.049）。［结论］ rs4646多态性位点可能会成为预测晚期乳腺癌阿那曲唑治疗疗效和预后的预测因子。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the association of the genetic polymorphism of CYP19A1 at rs4646 and rs10046on with the response to anastrozole in metastatic breast cancer. ［Methods］ Anastrozole was given to 272 women with hormone receptor-positive metastatic breast cancer. DNA was extracted from peripheral blood and genotyped for 2 variants in CYP19A1 gene. ［Results］ Two single nucleotide polymorphisms(SNP) (rs4646 and rs10046) were in Hardy-Weinberg equilibrium. Of 32 patients with complete response to anastrozole，24(75.0%) had a variant rs4646 SNP，whereas 60(78.9%) of 76 cases with progressive disease had a wild-type(GG) rs4646 SNP. The objective response categories were significantly different when segregated with respect to rs4646 status；significance was maintained after applying the Bonferroni correction.Time to progression was significantly improved in patients carrying the variant alleles of rs4646 compared to patients with the wild type allele(37.3 months vs 31.6 months，P=0.007). The rs4646 variant alleles were significantly associated with longer overall survival (16.4 months vs 13.52 months，P=0.049). This relationship was not observed in the rs10046 polymorphism. ［Conclusion］ The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with metastatic breast cancer treated with anastrozole. |
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