title: GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer.
abstract: 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.
authors.affiliation: Departamento de Obstetrícia e Ginecologia, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil drandrel@terra.com.br.
authors.forename: A L
authors.initials: AL
authors.lastname: Oliveira
authors.affiliation: Departamento de Obstetrícia e Ginecologia, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil.
authors.forename: F F
authors.initials: FF
authors.lastname: Oliveira Rodrigues
authors.affiliation: Departamento de Obstetrícia e Ginecologia, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil.
authors.forename: R E
authors.initials: RE
authors.lastname: Dos Santos
authors.affiliation: Departamento de Obstetrícia e Ginecologia, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil.
authors.forename: R L
authors.initials: RL
authors.lastname: Rozenowicz
authors.affiliation: Laboratório de Genética Molecular Humana, Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: M
authors.initials: M
authors.lastname: Barbosa de Melo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human