Oliveira A L, Oliveira Rodrigues F F, Dos Santos R E, Rozenowicz R L, Barbosa de Melo M
Departamento de Obstetrícia e Ginecologia, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil
Departamento de Obstetrícia e Ginecologia, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil.
Genet Mol Res. 2014 Jan 22;13(2):2521-30. doi: 10.4238/2014.January.22.9.
The glutathione S-transferase (GST) family comprises phase-II cellular detoxification enzymes that catalyze the conjugation of chemotherapy drugs to glutathione and act on the apoptotic pathway. The aim of this study was to determine whether polymorphisms of the GSTT1, GSTM1, and GSTP1 genes are associated with different rates of overall survival (OS) and disease-free survival (DFS) after neoadjuvant chemotherapy in the management of locally advanced breast cancer, using either simple or combined analyses, and in relation to the post-therapy axillary lymph node status. Forty women with invasive ductal carcinoma of the breast submitted to neoadjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide were genotyped for GSTT1, GSTM1, and GSTP1. Comparisons were performed for the three genes, either isolated or in pairs, in polymorphic or wild-type combinations. Finally, the OS and DFS of patients were analyzed with respect to axillary lymph node status and with respect to wild-type or polymorphic presentations of each gene. No statistically significant difference in OS and DFS was evident between women with wild-type or polymorphic forms of the genes, either isolated or in pairs, after neoadjuvant chemotherapy. By contrast, after treatment, lymph node-negative women had better OS and DFS only in the presence of polymorphisms of GSTP1, and improved DFS only in the presence of the polymorphic types of GSTT1 and GSTM1 compared to women with positive lymph nodes. The presence of polymorphic forms of GSTP1, GSTM1, and GSTT1 was crucial to conferring better OS and DFS among women with negative axillary lymph nodes.
谷胱甘肽S-转移酶（GST）家族由II期细胞解毒酶组成，这些酶催化化疗药物与谷胱甘肽结合，并作用于细胞凋亡途径。本研究的目的是确定GSTT1、GSTM1和GSTP1基因的多态性是否与局部晚期乳腺癌新辅助化疗后的总生存率（OS）和无病生存率（DFS）的不同发生率相关，采用单因素或联合分析，并与治疗后腋窝淋巴结状态相关。对40例接受5-氟尿嘧啶、表柔比星和环磷酰胺新辅助化疗的乳腺浸润性导管癌女性进行了GSTT1、GSTM1和GSTP1基因分型。对这三个基因进行了比较，无论是单独还是成对，以多态性或野生型组合形式。最后，分析了患者的OS和DFS与腋窝淋巴结状态以及每个基因的野生型或多态性表现的关系。新辅助化疗后，基因呈野生型或多态性形式的女性，无论是单独还是成对，其OS和DFS均无统计学显著差异。相比之下，治疗后，与腋窝淋巴结阳性的女性相比，腋窝淋巴结阴性的女性仅在存在GSTP1多态性时OS和DFS更好，仅在存在GSTT1和GSTM1多态性类型时DFS有所改善。GSTP1、GSTM1和GSTT1多态性形式的存在对于腋窝淋巴结阴性的女性获得更好的OS和DFS至关重要。
