Relationship of Polymorphisms of Glutathione S-Transferase GSTT1 and GSTM1 With the Response to Chemotherapy In Mexican Women with Advanced Breast Cancer

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 χi<sup>2</sup> 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

Association of the GSTM1 null polymorphism with breast cancer in a Mexican population

“…Soto-Quintana et al (2011) observed a tendency toward better chemotherapy response in patients with the null genotype of GSTT1 and GSTM1 polymorphisms and advanced BC. Additionally, an improved survival in patients with BC carrying the null GSTM1 genotype has been observed, and this has been explained by a better response to chemotherapeutic agents related to more effective cell killing, which in turn is related to the absence of a protective effect of the GSTM1 allele (Lizard-Nacol et al, 1999).…”