Genetic Predictors of Chemotherapy-Induced Cardiotoxicity in Leukemia: The Role of Sod2 And Comt Polymorphisms
Abstract
Chemotherapy-induced cardiotoxicity remains a major clinical challenge in patients with leukemias, contributing to reduced treatment tolerability and adverse long-term cardiovascular outcomes. Oxidative stress and neurohumoral dysregulation are key mechanisms underlying myocardial injury, while genetic variability may partly explain interindividual differences in susceptibility. This study aimed to evaluate the association of SOD2 (Val16Ala, rs4880) and COMT (Val158Met, rs4680) polymorphisms with the risk of cardiotoxic complications in leukemia patients receiving anticancer therapy. A total of 102 patients were stratified into subgroups with (n = 64) and without (n = 38) cardiological complications; 97 healthy individuals served as controls. Genotyping was performed using polymerase chain reaction with restriction fragment analysis. The SOD2 A allele showed a moderate association with cardiotoxicity, particularly for the homozygous A/A genotype (OR = 3.33; p = 0.12). In contrast, the COMT A (Met) allele demonstrated a strong and statistically significant association with cardiological complications (OR = 3.82; 95% CI: 1.97–7.42; p < 0.001), and the A/A genotype was associated with more than a fourfold increase in risk (OR = 4.45; p = 0.008). Combined analysis revealed a dose-dependent additive effect: carriage of two or more unfavorable alleles was associated with a more than fourfold increase in cardiotoxicity risk (OR = 4.22; p = 0.009). These findings support the role of pharmacogenetic factors in myocardial susceptibility and highlight the potential value of integrating SOD2 and COMT genotyping into personalized cardiovascular risk stratification strategies in leukemia patients.