Prognostic role of p53 gene polymorphism in risk assessment of anthracycline-induced cardiotoxicity

Abstract

To study the prognostic significance of polymorphism of the p53 gene (polymorphism Arg72Pro exon 4, rs1042522) on the development of cardiotoxic remodeling of the left ventricle and heart failure. A total of 176 women with breast cancer who received anthracycline antibiotics as part of polychemotherapeutic treatment regimens were examined. Based on the results of the survey, 12 months after the end of polychemotherapy, patients in the remission of the underlying disease were divided into 2 groups: patients with cardiotoxic remodeling (52 patients) and women with preserved heart function (124 patients). All patients before the start of the course of chemotherapy, in the dynamics of treatment with anthracyclines and after therapy with such were carried out the study of echocardiographic parameters. All the patients were taken genetic material, followed by typing alleles of the gene for the protein p53 (rs1042522). Analysis of echocardiographic parameters in patients 12 months after the completion of polychemotherapy in comparison with those before treatment showed a significant difference in the final systolic (33 mm [31; 35] and 28 mm [26; 31], p<0.00001) and terminal diastolic dimensions (51 mm [49; 54.5] and 44 mm [42; 48.5], p=0.0003), as well as a significant decrease in the left ventricular ejection fraction (54.5% [51.5; 58] and 65.5% [62; 70], p<0.00001) in the group of women with developed anthracycline cardiotoxicity. The presence of the Arg/Arg genotype was associated with the development of cardiotoxic myocardial damage during polychemotherapy (OR=3.86, 95% C.I.=1.45-10.26, p=0.005). The Pro/Pro genotype has proved to be a protective factor (OR=0.26, 95% C.I.=0.09-0.69, p=0.015). The conclusion. Predicting the cardiotoxicity of chemotherapy using the polymorphism of the p53 gene is an effective measure of early pre-symptom diagnosis of an increased risk of anthracyclineinduced cardiotoxicity.