ABSTRACT
Aim To evaluate the predictive significance of gene polymorphism in endothelin-1 type 2A receptor, NADPH oxidase, p53 protein, endothelial nitric oxide synthase, caspase 8, interleukin-1ß, tumor necrosis factor-α, superoxide dismutase-2, glutathione peroxidase-1, ß1-adrenoceptor, angiotensin-converting enzyme, and matrix metalloproteinase-3 (MMP-3) genes in evaluating the risk of anthracycline-induced cardiotoxicity (AIC) in women without concurrent cardiovascular diseases (CVD).Material and methods This study included 176 women aged 45.0 [42.0; 50.0] years with breast cancer without concurrent CVD who were scheduled for polychemotherapy (PCT) with anthracycline antibiotics. Echocardiography was performed for all patients at baseline and at 12 months after the end of PCT course. Genetic polymorphism was determined with the polymerase chain reaction.Results At 12 months, all patients were in remission of the underlying disease. They were retrospectively included into 2 groups: 1st group, 52 patients with AIC and 2nd group, 124 women without AIC symptoms. The development of AIC was associated with the presence of the p53 protein gene Argâ/âArg genotype (odds ratio (OR), 2.972; p=0.001), NOS3 gene Tâ/âT genotype (OR, 3.059; p=0.018), NADPH oxidase gene Tâ/âT genotype (OR, 2.753; p=0.008), GPX1 gene Câ/âC genotype (OR, 2.345; p=0.007), MMP-3 gene 5Aâ/â5A genotype (OR, 2.753; p=0.008), and ADRB1 gene Gâ/âG genotype (OR, 3.271; p=0.043).Conclusion Evaluation of genetic polymorphism in p53 protein (rs1042522), NOS3 (rs1799983), NADPH-oxidase (rs4673), GPX1 (rs1050450), ADRB1 (Arg389Gly, rs1801253), and MMP-3 (rs3025058) genes can be recommended for use prior to starting chemotherapy in women with breast cancer without CVD for assessing the risk of AIC. A maximum risk of cardiotoxicity is associated with the presence of the p53 protein gene Argâ/âArg genotype and NOS3 gene Tâ/âT genotype.
