天津医药

• 细胞与分子生物学 • 上一篇    下一篇

GSTM1、GSTT1及GSTP1(rs1695)基因多态性与乳腺癌蒽环和（或）紫杉类药物化疗血液毒性关系的研究

赵艳姣1,刘新兰2,黄英3,姜敏4   

  1. 1. 宁夏医科大学
    2. 宁夏医科大学总医院
    3. 宁夏医科大学总医院肿瘤医院
    4. 宁医大总院芯片中心
  • 收稿日期:2013-09-25 修回日期:2014-03-18 出版日期:2014-08-15 发布日期:2014-08-15
  • 通讯作者: 刘新兰

Correlation between Polymorphisms ofGSTM1, GSTT1andGSTP1(rs1695) on Hematologic Toxicities with Anthracycline/Paclitaxel-Based Chemotherapy in Breast Cancer

  • Received:2013-09-25 Revised:2014-03-18 Published:2014-08-15 Online:2014-08-15

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摘要：

【摘要】目的  研究乳腺癌外周血中谷胱甘肽转硫酶（GST）M1、GSTT1和GSTP1（rs1695）基因多态性与乳腺癌患者采用蒽环类和（或）紫杉类药物化疗发生血液毒性的关系。方法  应用多重PCR技术（M-PCR）和高分辨熔解曲线技术（HRM）检测3个基因在252例女性乳腺癌患者外周血中的基因多态性。结果  采用紫杉类、蒽环联合紫杉类药物化疗，携带GSTP1(rs1695)AG/GG的患者是发生Ⅲ~Ⅳ度中性粒细胞减低的危险因素(OR=6.111, 95%CI1.526~24.469, P＜0.05和OR=9.257, 95%CI2.903~29.522, P<0.01)，而GSTM1(+)与GSTM1(-)、GSTT1(+)与GSTT1(-)患者Ⅲ~Ⅳ度血液毒性的发生率差异均无统计学意义；采用蒽环类药物化疗，GSTM1(+)和GSTM1(-)、GSTT1(+)和GSTT1(-)、GSTP1AA和GSTP1AG/GG患者Ⅲ~Ⅳ度血液毒性发生率差异均无统计学意义(P>0.05)。结论  GSTP1(rs1695)基因多态性可作为预测乳腺癌患者采用紫杉类药物化疗发生中性粒细胞毒性的标志。

关键词: 乳腺肿瘤, 谷胱甘肽转移酶, 多态现象, 遗传, 聚合酶链反应, 化疗血液毒性, 高分辨熔解曲线技术, 抗肿瘤联合化疗方案

Abstract: [Abstract] Objective   To examine the effects of genetic polymorphisms in GSTM1, GSTT1 and GSTP1(rs1695) genes on hematologic toxicities of breast cancer patients receiving Anthracycline/Paclitaxel-based chemotherapy. Methods   The multiply PCR technique and High Resolution Melting method were used to examine 3 gene polymorphsim in 252 female breast cancers. Results   The GSTP1(rs1695) AG/GG genotype was a risk factor for Ⅲ-Ⅳ degree of neutrophil toxicity when patients received Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy(OR=6.111, 95% CI:1.526~24.469, P<0.05 and OR=9.257, 95% CI:2.903-29.522, P<0.01), while there were no statistic difference on Ⅲ-Ⅳ degree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-) patients receiced Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy(P>0.05); there was still no statistic difference on Ⅲ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-), GSTP1AA and GSTP1AG/GG patients receiced Anthracycline-based chemotherapy(P>0.05). Conclusion   The genetic polymorphisms in GSTP1(rs1695) can be a gene markers for forecasting the chemotherapy neutropenia toxicities of breast cancer patients receiving Paclitaxel-based chemotherapy.

Key words: breast neoplasms, glutathione transferase, polymorphism, genetic, Polymerase chain reaction, chemotherapy hematologic toxicities, High Resolution Melting., 抗肿瘤联合化疗方案