Synergistic Effect of Sod2 And Cat Gene Polymorphisms in The Development of Cardiotoxic Complications

Cardiotoxic complications remain one of the major limitations of modern antitumor therapy, significantly affecting treatment outcomes and long-term prognosis. Oxidative stress plays a key role in the pathogenesis of chemotherapy-induced myocardial damage, while genetic variability in antioxidant defense systems may determine individual susceptibility to cardiotoxic effects. The present study aimed to evaluate the combined influence of SOD2 and CAT (G262A) gene polymorphisms on the risk of cardiotoxic complications in patients receiving chemotherapy. A total of 102 patients undergoing antitumor treatment were included and divided into subgroups with (n=64) and without (n=38) cardiological complications; 97 healthy individuals served as controls. Genotyping was performed using polymerase chain reaction, and associations were assessed by calculating odds ratios (OR) with 95% confidence intervals (CI). Carriage of the SOD2 A allele was associated with an increased risk of cardiotoxic complications (OR=1.32; p=0.03). The CAT 262A allele demonstrated an independent association with cardiotoxicity (OR=2.03; p=0.041). The highest risk was observed in patients carrying unfavorable alleles in both genes simultaneously, with a more than threefold increase in cardiotoxic complications (OR=3.46; p=0.004), indicating a synergistic effect. A dose-dependent relationship between the number of unfavorable alleles and cardiotoxic risk was identified. These findings suggest that combined analysis of SOD2 and CAT polymorphisms may improve risk stratification and support the development of personalized cardioprotective strategies in patients receiving potentially cardiotoxic chemotherapy.

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