Abstract
To evaluate the predictive value of GST gene polymorphisms with regard to prognosis of breast cancer patients receiving neoadjuvant chemotherapy. A total of 159 patients were included in our study between January 2005 and January 2007. All the patients were followed up until January 2012. Genotyping was based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. Patients with null GSTM1 and GSTP1 Val/Val genotypes had significantly had better response rates to chemotherapy when compared with non-null GSTM1 and GSTP1 Ile/ Ile genotypes (OR=1.96 and OR=2.14, respectively). Patients with the GSTM1 null genotype had a longer average survival time and significantly lower risk of death than did those with non-null genotypes (HR=0.66). Similarly, those carrying the GSTP1 Val/Val genotype had 0.54- fold the risk of death of those with GSTP1 Ile/ Ile (HR=0.54). A significant association was found between GSTM1 and GSTP1 gene polymorphisms and clinical outcomes in breast cancer cases.
Highlights
Breast cancer is by far the most frequent cancer among women with an estimated 1.38 million new cancer cases diagnosed in 2008 (23% of all cancers), and ranks second overall (10.9% of all cancers)
A significant association was found between GSTM1 and GSTP1 gene polymorphisms and clinical outcomes in breast cancer cases
The present study investigates the association and clinical outcomes, but no association was found between Glutathione S-transferases (GSTs) polymorphisms, GSTM1, GSTT1 and between GSTT1 polymorphism and risk of death from
Summary
Breast cancer is by far the most frequent cancer among women with an estimated 1.38 million new cancer cases diagnosed in 2008 (23% of all cancers), and ranks second overall (10.9% of all cancers). Anthracycline-based chemotherapy regimens are preferred for downstaging breast cancer tumors (Bafaloukos et al, 2005). Response to chemotherapy cannot be predicted for patients, but the polymorphism in genes encoding for metabolizing enzymes and drug transporters can affect drug efficacy and toxicity (Bosh et al, 2006). 4 major subfamilies of GSTs can be distinguished and are designated as GSTa, GSTμ, GSTθ and GSTπ. Each of these subfamilies is composed of several members, some of which display genetic polymorphism. Homozygozity of GSTM1 and GSTT1, members of GSTμ and GSTθ, leads to absence of phenotypic enzyme activity. The polymorphism of GSTP1 at codon 105 (IIe105Val), a member of GSTπ subfamily, shows different catalytic activities (Mishra et al, 2001)
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