Association of GSTO1 A140D and GSTO2 N142D Gene Variations with Breast Cancer Risk

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Polymorphisms in glutathione S-transferase (GST) genes may contribute to breast cancer risk. The aim of this study was to investigate any association of two common GSTO1 A140D and GSTO2 N142D gene polymorphisms with breast cancer risk in an Iranian population followed by a protein structure analysis. </span></span><strong><span style="font-size: small;">Materials and Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">In the case-control study, 303 subjects comprising 153 women with breast cancer and 150 healthy controls were included. Genotypes of GSTO1 A140D and GSTO2 N142D polymorphisms were assessed by PCR-RFLP. Bioinformatics tools were employed to evaluate the damaging effects of A140D and N142D on the structures of GSTO1 and GSTO2 proteins. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Our genetic association study revealed that the GSTO1 A140D polymorphism was associated with breast cancer in a dominant model (OR= 1.75, 95%CI= 1.07-2.86, p= 0.026). Also, the A allele was </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">significantly associated with breast cancer risk (OR= 1.69, 95%CI= 1.09-2.60, p= 0.018). With regard to the N142D polymorphism, there were significant associations between the GG genotype (OR= 2.20, 95%CI= 1.14-4.27, p= 0.019) </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">and the G allele (OR= 1.47, 95%CI= 1.06-2.05, p= 0.021) and risk of breast cancer. Structural analysis revealed that A140D and N142D polymorphisms cause changes in both primary and secondary structures of GSTO1 and GSTO2, respectively. </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Based on our results, GSTO1 A140D and GSTO2 N142D polymorphisms could be genetic risk factors for breast cancer, but further studies with larger sample sizes focusing on different ethnicities are needed to obtain more comprehensive results. </span></span>