Studying the association between some genetic polymorphisms and Doxorubicin-Induced Cardiotoxicity

Abstract

<p><span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: EN-US;">Anthracyclines are a crucial component of chemotherapy regimens used to treat a range of malignancies in children and adults. However, cardiac dysfunction and heart failure frequently limit the therapeutic efficacy of anthracyclines. The risk of heart dysfunction increases with increasing doses of anthracycline. Cardiotoxicity is a challenging side effect of DOX, which is cumulative and irreversible; this necessitates assessing the cardiac functions in cancer patients before and after the use of<span style="mso-spacerun: yes;">&nbsp;&nbsp; </span></span><span dir="RTL" style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;"><span style="mso-spacerun: yes;">&nbsp;</span></span><span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: EN-US;">DOX to avoid permanent cardiac damage. Serial measurements of left ventricle ejection fraction (LVEF) are commonly used for cardiac monitoring during anthracycline treatment.</span><span dir="RTL" style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;"> </span><span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: EN-US;">In some studies, cardiotoxicity was defined as LVEF decrease by an absolute 10% and/or below 55%; in others, cardiotoxicity was defined as a decrease below 45%. A serious disadvantage of this test is radioactivity exposure and the low predictability of pre-symptomatic cardiac damage. Blood cardiac biomarkers, such as cardiac troponins and B-type natriuretic peptide (BNP), have been used in heart failure diagnostics</span><span dir="RTL" lang="AR-EG" style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-EG;">.</span><span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: EN-US;"> Susceptibility to DOX cardiotoxicity is largely individual, with some patients developing cardiomyopathy at low doses and others tolerating much higher cumulative doses, and this may suggest the presence of genetic predisposition factors. Genetic variations in <a name="_Hlk84441804"></a>CBR3 and ABCC1 genes were suggested to contribute to DOX adverse effects.</span><span dir="RTL" style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;"> </span><span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: EN-US;">This review highlights the genetic basis for anthracycline-related cardiac dysfunction, focuses on particular genes that have been implicated in innate predisposition to ACT, and assessment of cardiotoxicity.</span></p>