EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients
Abstract Background Breast cancer is the leading cause of cancer-related deaths globally, with taxanes being the most commonly used chemotherapeutic agents. However, adverse effects like myelosuppression, neuropathy, and hypersensitivity reactions exist. Objective To find the association between gen...
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| Format: | Article |
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SpringerOpen
2025-06-01
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| Series: | Future Journal of Pharmaceutical Sciences |
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| Online Access: | https://doi.org/10.1186/s43094-025-00827-1 |
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| author | Amira B. Kassem Amira Abdelmonem Ahmed Noha A. El‑Bassiouny Gamal Omran Mahmoud Mohamed Kamel Ahmed El Bastawisy Nermeen Nabeel Abuelsoud |
| author_facet | Amira B. Kassem Amira Abdelmonem Ahmed Noha A. El‑Bassiouny Gamal Omran Mahmoud Mohamed Kamel Ahmed El Bastawisy Nermeen Nabeel Abuelsoud |
| author_sort | Amira B. Kassem |
| collection | DOAJ |
| description | Abstract Background Breast cancer is the leading cause of cancer-related deaths globally, with taxanes being the most commonly used chemotherapeutic agents. However, adverse effects like myelosuppression, neuropathy, and hypersensitivity reactions exist. Objective To find the association between genetic polymorphisms in SOD2 rs4880 and EPHA5 rs7349683 and taxane-induced neurotoxicity, also to prospectively evaluate the usefulness of serum neurofilament light chain (sNFL) levels as an early biomarker of development neurotoxicity in different genotypes. Methods One hundred breast cancer patients prospectively received taxane treatment. Blood samples were collected, and SOD2 and EPHA5 gene polymorphisms were detected using real-time PCR. All patients were assessed using the Common Terminology Criteria for Adverse Events v 5.0 score, and the biomarker was measured from serum using an enzyme immunosorbent assay at baseline and three months after taxanes treatment. Results The detected SOD2 (rs4880) genetic polymorphisms were AA (39%), AG (49%), GG (12%), CC (49%), TC (42%), and TT (9%) in EPHA5 (rs7349683). A statistically significant difference existed between EPHA5 C > T genotypes regarding the NFL levels and delta NFL (p value = 0.000 and 0.010, respectively). Also, there was a significant association between different EPHA5 C > T genotypes and neurotoxicity grades post-taxanes treatment (p value = 0.010). There was a statistically significant difference in fatigue associated with the EPHA5 gene (p value = 0.011). Conclusion Detecting EPHA5 genetic polymorphisms before administering taxanes is highly recommended for assessing neurotoxicity risk. NFL measurement is recommended to be used in the early identification of taxane-induced neurotoxicity. |
| format | Article |
| id | doaj-art-ec336a2e4e204b7b90b9eca22c7eeb52 |
| institution | Kabale University |
| issn | 2314-7253 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Future Journal of Pharmaceutical Sciences |
| spelling | doaj-art-ec336a2e4e204b7b90b9eca22c7eeb522025-08-20T03:47:24ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532025-06-0111111310.1186/s43094-025-00827-1EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patientsAmira B. Kassem0Amira Abdelmonem Ahmed1Noha A. El‑Bassiouny2Gamal Omran3Mahmoud Mohamed Kamel4Ahmed El Bastawisy5Nermeen Nabeel Abuelsoud6Department of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, Damanhur UniversityDepartment of Clinical Pharmacy and Practice Pharmacy, Faculty of Pharmacy, Egyptian Russian UniversityDepartment of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, Damanhur UniversityBiochemistry Department, Faculty of Pharmacy, Damanhur UniversityDepartment of Clinical Pathology, National Cancer Institute, Cairo UniversityDepartment of Medical Oncology, National Cancer Institute, Cairo UniversityPharmacy Practice Department, Faculty of Pharmacy, Heliopolis UniversityAbstract Background Breast cancer is the leading cause of cancer-related deaths globally, with taxanes being the most commonly used chemotherapeutic agents. However, adverse effects like myelosuppression, neuropathy, and hypersensitivity reactions exist. Objective To find the association between genetic polymorphisms in SOD2 rs4880 and EPHA5 rs7349683 and taxane-induced neurotoxicity, also to prospectively evaluate the usefulness of serum neurofilament light chain (sNFL) levels as an early biomarker of development neurotoxicity in different genotypes. Methods One hundred breast cancer patients prospectively received taxane treatment. Blood samples were collected, and SOD2 and EPHA5 gene polymorphisms were detected using real-time PCR. All patients were assessed using the Common Terminology Criteria for Adverse Events v 5.0 score, and the biomarker was measured from serum using an enzyme immunosorbent assay at baseline and three months after taxanes treatment. Results The detected SOD2 (rs4880) genetic polymorphisms were AA (39%), AG (49%), GG (12%), CC (49%), TC (42%), and TT (9%) in EPHA5 (rs7349683). A statistically significant difference existed between EPHA5 C > T genotypes regarding the NFL levels and delta NFL (p value = 0.000 and 0.010, respectively). Also, there was a significant association between different EPHA5 C > T genotypes and neurotoxicity grades post-taxanes treatment (p value = 0.010). There was a statistically significant difference in fatigue associated with the EPHA5 gene (p value = 0.011). Conclusion Detecting EPHA5 genetic polymorphisms before administering taxanes is highly recommended for assessing neurotoxicity risk. NFL measurement is recommended to be used in the early identification of taxane-induced neurotoxicity.https://doi.org/10.1186/s43094-025-00827-1Breast cancerEPHA5SOD2Genetic polymorphismsNeurotoxicityTaxanes |
| spellingShingle | Amira B. Kassem Amira Abdelmonem Ahmed Noha A. El‑Bassiouny Gamal Omran Mahmoud Mohamed Kamel Ahmed El Bastawisy Nermeen Nabeel Abuelsoud EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients Future Journal of Pharmaceutical Sciences Breast cancer EPHA5 SOD2 Genetic polymorphisms Neurotoxicity Taxanes |
| title | EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients |
| title_full | EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients |
| title_fullStr | EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients |
| title_full_unstemmed | EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients |
| title_short | EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients |
| title_sort | epha5 and sod2 genetic variants and their link to neurofilament light chain early detection of taxane induced neurotoxicity in egyptian breast cancer patients |
| topic | Breast cancer EPHA5 SOD2 Genetic polymorphisms Neurotoxicity Taxanes |
| url | https://doi.org/10.1186/s43094-025-00827-1 |
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