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

摘要

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 Multiply PCR technique and High Resolution Melting method were used to examine these 3 genes polymorphsim in female breast cancers (n=252). Results The GSTP1(rs1695) AG/GG genotype was a risk factor forⅢ-Ⅳdegree of neu-trophil 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). There were no statistic differ-ence onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-) patients after they receiced Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy( P>0.05);There was no statistic difference onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-), GSTP1AA and GSTP1AG/GG patients after they receiced Anthracycline-based chemotherapy (P>0.05). Conclusion The genetic polymorphisms in GSTP1(rs1695) can be used as a gene marker for forecasting the chemotherapy, inducing neutrope-nia toxicities in breast cancer patients receiving Paclitaxel-based chemotherapy.%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%CI 1.526~24.469, P＜0.05和OR=9.257,95%CI 2.903~29.522, 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。