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.

Chemotherapy-induced cardiotoxicity, leukemia, oxidative stress

Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229–4361. doi:10.1093/eurheartj/ehac244.

Curigliano G, Lenihan D, Fradley M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31(2):171–190.

Armenian SH, Lacchetti C, Barac A, et al. Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2017;35(8):893–911. doi:10.1200/JCO.2016.70.5400.

Murabito A, Hirsch E, Ghigo A. Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer? Front Cardiovasc Med. 2020;7:35.

Xie S, et al. An update of the molecular mechanisms underlying anthracycline-induced cardiotoxicity and potential therapeutic targets. Front Pharmacol. 2024.

Ahmed AM, et al. Study of the association of EDN1 rs5370 polymorphism with cardiovascular and renal diseases — role of endothelin-1 in vascular dysfunction and disease pathophysiology. J Clin Genet Cardiovasc. 2025; (EDN1, ET-1 and CV disease mechanisms)

Иноятова С.О., et al. Взаимодействие полиморфизмов генов SOD2, EDN1 (rs5370) и eNOS: влияние на цереброваскулярные заболевания и окислительный стресс. Biomedical and Pharmacology Journal. 2025;

Lazurova Z, et al. Association of polymorphisms in endothelin-1 and endothelin receptor A genes with tilt-induced syncope and autonomic activity. Physiol Res. 2022; 71:93–104.

Hashemi M, et al. Association of endothelin-1 gene polymorphisms with metabolic and cardiovascular traits. Clin Genet Cardiovasc. 2025;

Petyunina OV, et al. Risk factors and endothelin-1 (rs5370) polymorphism in myocardial infarction with ST-segment elevation. Ukr Med Biol J. 2019;2:

Nepal G, et al. Association between EDN1 Lys198Asn polymorphism and ischemic stroke: a meta-analysis. Eur J Genet Cardiovasc. 2019;

Nawaz SK, et al. Association of EDN1 rs5370 variant with coronary artery disease in a South Asian cohort. Pure Appl Biol. 2021;10 (4):1427–1435.

Davenport AP, et al. Endothelin system pharmacology — molecular and clinical insights into endothelin-1 receptor physiology and pathophysiology. Pharmacol Rev. 2016;68(2):357–418.

Torabi P, Ricci F, Hamrefors V, et al. Impact of cardiovascular neurohormones on onset of vasovagal syncope by head-up tilt. J Am Heart Assoc. 2019;8: e012559.