Cardiovascular toxicity in patients with oncohematological diseases: genetic predictors study.

Abstract

Background: The aim is of this study to identify genetic single nucleotide polymorphisms associated with cardiovascular (CV) toxicity in patients of oncohematological profile receiving antitumor immune chemotherapy.

Methods: In single-center prospective study were included 34 patients with the diagnosis of non-Hodgkin's B-cell follicular lymphoma. All of them received R-CHOP scheme immune chemotherapy. Patients were divided into two groups up to the appearance of CV toxicity during the treatment: main group - patients with CV toxicity (mean age 42.4±2.8, three men [25%]), control group - without it (mean age 39.8±1.7, of which eight men [36%]). CV toxicity has been defined by the presence of CV symptoms associated to a reduction of left ventricular ejection fraction (LVEF) >10% from baseline or in absolute lower than 53% and/or a decrease in LV longitudinal strain >12% from baseline and/or an increase in NT-proBNP>125 pg/mL.

Results: This study presents the identified genetic features in patients with an oncohematological profile in the context of the occurrence of CV toxicity during the treatment of malignant neoplasms. Variants rs1879257 of the ABCC5 gene, rs13224758 of the PRKAG2 gene, rs10925391 of the RYR2 gene and rs4149178 of the SLC22A7 gene significantly increased the risk of developing CV toxicity in the target group of patients by 5-6 times. In addition, the study showed that the rs2032582 ABCB1 gene and rs3729856 GATA4 gene variants had the opposite effect and reduced the risk of developing CV complications, having a protective effect on the CV system.

Conclusions: The results of this study endorse the possibility of performing a genetic screening before anticancer immunochemotherapy as a future tool for stratifying patients with an oncohematological profile and minimizing CV toxicity. However, further studies are needed to confirm the diagnostic and prognostic role of the above identified genetic variants.