Anthracycline-induced cardiotoxicity in women without cardiovascular diseases: molecular and genetic predictors

Abstract

Objective

To evaluate role of molecular (endothelin-1, soluble Fas-L, NT-proBNP, TNF-α, interleukin-1β,) and genetic factors (NOS3 (rs1799983), EDNRA (C + 70G, rs5335), NADPH oxidase (C242T, rs4673), p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522), NOS3 (Glu298Asp, rs1799983), Caspase 8 (CASP8, rs3834129 and rs1045485), interleukin-1β gene (Il-1β, rs1143634), TNF-α gene (rs1800629), SOD2 (rs4880), GPX1 (rs1050450) in development of anthracycline-induced cardiotoxicity (AIC) in women without cardiovascular diseases.

Methods

A total of 176 women with breast cancer and without cardiovascular diseases who received anthracyclines were enrolled in the study. After the 12 months of chemotherapy (CT), all patients were divided into two groups: group 1 (n = 52) comprised patients with AIC, group 2 (n = 124) comprised those without it.

Results

Based on ROC-analysis, levels of endothelin-1 of ≥9.0 pg/mL (AUC of 0.699), sFas-L of ≥98.3 ng/mL (AUC of 0.990), and NT-proBNP of ≥71.5 pg/mL (AUC of 0.994;) were identified as a cut-off values predicting AIC during 12 months after CT. Whereas, NT-proBNP and sFas-L were more significant predictors than endothelin-1 (p < 0.001). The development of AIC was significantly related to Arg/Arg of p53 protein gene (OR = 2.972; p = 0.001), T/T of NOS3 gene (OR = 3.059, p = 0.018), T/T of NADPH oxidase gene (OR = 2.753, p = 0.008), and C/C of GPX1 (OR = 2.345; p = 0.007).

Conclusion

Evaluation of polymorphisms genes of p53 (rs1042522), NOS3 (rs1799983), GPX1 (rs1050450), and NADPH oxidase (rs4673) can be recommended before CT for the risk assessment of AIC development. The serum levels of NT-proBNP and soluble Fas-L after CT may be considered as non-invasive biomarkers for prediction of AIC development during the 12 months.

Keywords:

• Anthracycline-induced cardiotoxicity
• gene polymorphisms
• biomarkers
• soluble Fas-L
• NT-proBNP
• prediction

Acknowledgement

The data of this study was presented as oral abstract presentation at ESC Preventive Cardiology 2021 (15-17 April, 2021; online congress).

Disclosure statement

The authors declare that there is no conflict of interest. The authors state that they have obtained appropriate approval of the local Ethics Committee and have followed the principles outlined in the Declaration of Helsinki for all human research. Informed consent has been obtained from the participants involved.