CELF4 (rs1786814) gene polymorphism and speckle-tracking Echocardiography for cardiovascular complications in childhood cancer survivors

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2024年7月24日

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Seham M. Ragab,
Mahmoud A. El-Hawy,
Sally M. El-Hefnawy,
Hend M. A. El –Deeb,
Amany S. Elfalah,
Asmaa A. Mahmoud

摘要

Background

Despite a well-known dose-dependent association between the risk of cardiac dysfunction and anthracycline, the risk of cardiac dysfunction for any given anthracycline dose varies between patients. So, we assessed CELF4 (rs1786814) gene polymorphism on anthracycline-related cardiotoxicity in childhood cancer survivors (CCS).

Methods

This comparative cross-sectional study included 53 CCS who had regular follow-up visits at the Pediatric Oncology Unit, Menoufia University Hospital. CELF4 (rs1786814) gene polymorphism and conventional and speckle-tracking Echocardiography were done for all survivors.

Results

Regarding CELF4 (rs1786814) genotypes, significant differences existed between the studied groups with a predominance of GG homozygous mutation. For Echocardiographic findings, the ejection fraction and end-systolic diameter compared to the control group, were significantly lower in the survivors group. Speckle- tracking Echocardiography showed a significant difference regarding (GLPS-A4C) and (GLPS-LAX), with no significant difference regarding (GLPS-A2C), (GLPS-Avg) and left atrium between the studied groups. Multivariate logistic regression analysis illustrated a statistically significant relation between cumulative anthracycline dose >300 mg/m² and CLEF4 (rs1786814) genotypes (GG and GA) and the risk of cardiotoxicity with more significance in GG mutation.

Conclusion

Early detection of ventricular dysfunction in CCS with subclinical cardiotoxicity with regular follow-up is promising before the development of life-threatening complications.

Impact

Early detection of anthracycline-related cardiotoxicity in childhood cancer survivors (CCS) after finishing chemotherapy.

CLEF4 (rs1786814) GG variant is more significant in CCS exposed to high-dose anthracycline.

GLPS holds promise as an early predictor of late left ventricular dysfunction and subclinical cardiotoxicity in CCS.