Abstract
Introduction: Breast cancer is a common disease diagnosed in Mexican women and the first leading cause of death [1]. Heterogeneity in patients’ response to treatment is consistently observed across populations. Glutathione S-transferases (GSTs) are involved in the metabolism of environmental carcinogens, reactive oxygen species and chemotherapeutic agents by catalyzing the glutathione with electrophilic compounds. The deletion of GSTT1 and GSTM1 genes result in loss of enzyme activity. A few studies evaluated the response to treatment and the polymorphisms of GSTT1 and GSTM1. The aim of this work is to make the association of the null polymorphisms of GSTT1 and GSTM1 with the response to chemotherapy basically doxorubicin and cyclophosphamide. Methods: The genotyping of thirty patients with breast cancer was made with the Polymerase chain reaction, to identify the polymorphisms of GSTT1 and GSTM1. We determine the status of Her-2 neu, estrogen and progesterone receptors, then the response to treatment was made with an ultrasound and pathological data. We made the association with the χi2 statistics using a p≤0.05. Results: Using the Sigma Stat 3.5 program and the chi-squared analysis, we do not observe a significant association with the GSTT1+/GSTM1+, GSTT1-/GSTM1+ and GSTT1-/GSTM1-polymorphisms and the better or worse response to cyclophosphamide and doxorubicin. With the Her-2 neu, estrogen and progesterone receptors status, we neither found an association with the response to the therapy. Conclusion: This study suggests that GSTT1 and GSTM1 polymorphisms have no statistical significance between the genotype of women with advanced breast cancer and the response to neoadjuvant chemotherapy, but we can see a clear tendency toward better response with the null genotype.
Highlights
Breast cancer is a common disease diagnosed in Mexican women and the first leading cause of death [1]
This study suggests that GSTT1 and GSTM1 polymorphisms have no statistical significance between the genotype of women with advanced breast cancer and the response to neoadjuvant chemotherapy, but we can see a clear tendency toward better response with the null genotype
The aim of this work is making the association of the null polymorphisms of GSTT1 and GSTM1, the status of HER2, estrogen and progesterone receptors with the response to chemotherapy, specific the treatment with doxorubicin associated to cyclophosphamide in Mexican women with advanced breast cancer
Summary
Breast cancer is a common disease diagnosed in Mexican women and the first leading cause of death [1]. The aim of this work is to make the association of the null polymorphisms of GSTT1 and GSTM1 with the response to chemotherapy basically doxorubicin and cyclophosphamide. Results: Using the Sigma Stat 3.5 program and the chi-squared analysis, we do not observe a significant association with the GSTT1+/GSTM1+, GSTT1–/GSTM1+ and GSTT1–/GSTM1– polymorphisms and the better or worse response to cyclophosphamide and doxorubicin. Conclusion: This study suggests that GSTT1 and GSTM1 polymorphisms have no statistical significance between the genotype of women with advanced breast cancer and the response to neoadjuvant chemotherapy, but we can see a clear tendency toward better response with the null genotype. It is known that they are crucial for the cell defense system They are phase II enzymes involved in conjugation of a wide range of xenobiotics [6]. GSTs are induced under conditions of oxidative stress [7], the mechanism of detoxification is by conjugation to reduced glutathione (GSH), a tripeptide consisting of glycine, glutamic acid and cysteine, with electrophilic compounds, reducing the harmful agents to lower toxic levels and water soluble products [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]
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