谷胱甘肽S转移酶基因多态性与乳腺癌化疗疗效的关系

Association of GSTs gene polymorphism with response to chemotherapy in breast cancer

目的观察乳腺癌患者谷胱甘肽S转移酶(GSTs)基因多态性与化疗敏感性之间的关系。方法收集接受蒽环类为基础化疗且具有完整疗效评价资料的132例原发性乳腺癌患者化疗前静脉血,检测GSTP1(A314G)、GSTA1(C69T)、GSTM1(缺失)和GSTT1(缺失)基因型,开展基因多态性与乳腺癌化疗疗效关系的分析。结果在132例含蒽环类方案的化疗患者中,GSTP1基因型AA的有效率(56.3%)明显低于AG和GG(75.0%和100.0%;χ2=6.842,P<0.01),且A等位基因与GSTT1(未缺失)及GSTT1(未缺失)+GSTM1(未缺失)+GSTA1携带野生型的组合,有效率为54.5%或46.9%,也明显低于其相应各组(72.6%,χ2=4.475,P<0.05及69.2%,χ2=5.100,P<0.05)。其中90例患者同时接受紫杉醇治疗,其GSTM1未缺失者的有效率(50.0%)低于缺失者的有效率(76.5%,χ2=6.722,P=0.01),且未缺失者与GSTT1(未缺失)+GSTP1携带野生型+GSTA1携带野生型组合的有效率为41.7%,也明显低于其他患者(74.6%,χ2=8.128,P<0.01)。结论乳腺癌患者GSTs基因多态性检测可能有助于乳腺癌蒽环类和/或紫杉醇类药物疗效的预测。

Objective To investigate the relationship between glutathione S-transferases（GSTs） gene polymorphism and chemotherapeutic responses in breast cancer patients.Methods Blood specimens were collected from 263 breast cancer patients before chemotherapy and were genotyped for GSTP1（A314G）,GSTA1（C69T）,GSTM1（null） and GSTT1（null）.The correlation of the GST polymorphisms with chemotherapy responses was analyzed in 132 breast cancer patients who received anthracycline-based chemotherapy and preserved the intact follow-up information after treatment.Results In the 132 patients with anthracycline-based chemotherapy,GSTP1 AA genotype（56.3%） showed lower response than AG and GG genotype（75.0% and 100.0%;χ2 = 6.842,P 0.05）.The efficient rate of the combination of GSTP1 wild-type allele with GSTT1（present）,or with GSTT1（present） plus GSTM1（present） plus GSTA1 wild-type allele was 54.0% or 46.9% respectively,which was also lower than that of the corresponding groups（72.6%,χ2 = 4.475,P 0.05 or 69.2%,χ2 = 5.100,P 0.05）.In the 132 patients,90 cases received taxane treatment simultaneously.The efficient rate（50.0%） of the GSTM1（present） genotype was lower than that of GSTM1-deleted null genotype（76.5%,χ2 = 6.722,P 0.05）.In addition,the efficient rate（41.7%） of the combination of GSTM1（present） with GSTT1（present） plus GSTP1 wildtype allele plus GSTA1 wild-type allele was lower than that of other patients（74.6%,χ2 = 8.128,P 0.01）.Conclusions The analysis of GSTs gene polymorphisms in breast cancer patients may be valuable for predicting the response to anthracycline or/and taxane chemotherapy for the breast cancer patients,and further study should be needed.