Characterization of Novel Non-Synonymous Genomic Variants Altering Drug Response of DNA Topoisomerase II Alpha

Abstract

Background: DNA topoisomerase II alpha (Top2-α) enzyme is an important target for many anticancer drugs. A variety of TOP2A genomic variants has been found associated with the development of drug resistance to this enzyme. Methods: Here, we have characterized 2 non-synonymous single nucleotide polymorphisms (nsSNPs) including rs762022284 and rs764177670 in TOP2A gene, which could affect its response to Amsacrine and Mitoxantrone as important inhibitors of the enzyme. The nsSNPs were genotyped in the Iranian population and the data were analyzed, using PLINK and PICcalc programs. Results: Genotyping data indicated the allele frequency of 0.30 (PIC = 0.42) and 0.05 (PIC = 0.09) for rs762022284 and rs764177670, respectively. Conclusions: The data suggested that the presence of rs762022284 and rs764177670 nsSNPs could affect Top2-α response to Amsacrine and Mitoxantrone, indicating the necessity of consideration of population-dependent genotypes in cancer chemotherapy, using these drugs.