The impact of CBR3 (rs1056892) and ABCC1 (rs45511401) genetic polymorphisms on doxorubicin-induced cardiotoxicity and the potential role of brain natriuretic peptide as an early cardiac biomarker in breast cancer patients.
Enas A El-Shorbagy, Noha A El-Bassiouny, Amira B Kassem, Ahmad Salahuddin, Mahmoud Mohamed Kamel, Ahmed El Bastawisy, Nermeen Nabeel Abuelsoud
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Abstract
Background: Doxorubicin (DOX), a potent antineoplastic drug, can induce cardiotoxicity through its cardiotoxic metabolites catalyzed by CBR 3 and its accumulation in cardiac tissue via the ABCC1 transporter. Here, we investigated CBR3 and ABCC1 genetic polymorphisms affecting doxorubicin cardiotoxicity in breast cancer patients and explored the potential role of brain natriuretic peptide (BNP) as an early cardiac biomarker.
Methods: One hundred Breast cancer patients are receiving DOX treatment. Blood samples were analyzed for CBR3 and ABCC1 gene polymorphisms and echocardiography and BNP biomarkers were used to assess cardiotoxicity at baseline and three months post-DOX treatment.
Results: Following the DOX treatment, CBR3 genotypes showed significant differences in BNP levels and delta BNP (p = 0.001 and 0.014, respectively). There was a significant association between different CBR3 genotypes and BNP levels after DOX (p = 0.001) and delta BNP (p = 0.01), with AA genotypes associated with cardiotoxicity. ABCC1 was not associated significantly with cardiotoxicity (p = 0.67). There was a statistically significant difference between CBR3 genotypes and the occurrence of anemia (p = 0.023).
Conclusion: Detecting CBR3 genetic polymorphisms is crucial for assessing cardiotoxicity before administering DOX, and monitoring BNP levels helps early detection. CBR3 is also associated with DOX anemia.
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