دورية أكاديمية
Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients.
| العنوان: | Exome array analysis identifies ETFB as a novel susceptibility gene for anthracycline-induced cardiotoxicity in cancer patients. |
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| المؤلفون: | Ruiz-Pinto, Sara, Pita, Guillermo, Martín, Miguel, Alonso-Gordoa, Teresa, Barnes, Daniel R, Alonso, María R, Herraez, Belén, García-Miguel, Purificación, Alonso, Javier, Pérez-Martínez, Antonio, Cartón, Antonio J, Gutiérrez-Larraya, Federico, García-Sáenz, José A, Benítez, Javier, Easton, Douglas F, Patiño-García, Ana, González-Neira, Anna |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1007/s10549-017-4497-9 Breast Cancer Res Treat |
| سنة النشر: | 2018 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Anthracyclines, Chronic cardiotoxicity, ETFB, Long-term cancer survivors, Low-frequency variants, Adult, Aged, Breast Neoplasms, Cancer Survivors, Cardiotoxicity, Electron-Transferring Flavoproteins, Exome, Female, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Genetic Predisposition to Disease, Heart Failure, Humans, Middle Aged, Mitochondria |
| الوصف: | PURPOSE: Anthracyclines are widely used chemotherapeutic drugs that can cause progressive and irreversible cardiac damage and fatal heart failure. Several genetic variants associated with anthracycline-induced cardiotoxicity (AIC) have been identified, but they explain only a small proportion of the interindividual differences in AIC susceptibility. METHODS: In this study, we evaluated the association of low-frequency variants with risk of chronic AIC using the Illumina HumanExome BeadChip array in a discovery cohort of 61 anthracycline-treated breast cancer patients with replication in a second independent cohort of 83 anthracycline-treated pediatric cancer patients, using gene-based tests (SKAT-O). RESULTS: The most significant associated gene in the discovery cohort was ETFB (electron transfer flavoprotein beta subunit) involved in mitochondrial β-oxidation and ATP production (P = 4.16 × 10-4) and this association was replicated in an independent set of anthracycline-treated cancer patients (P = 2.81 × 10-3). Within ETFB, we found that the missense variant rs79338777 (p.Pro52Leu; c.155C > T) made the greatest contribution to the observed gene association and it was associated with increased risk of chronic AIC in the two cohorts separately and when combined (OR 9.00, P = 1.95 × 10-4, 95% CI 2.83-28.6). CONCLUSIONS: We identified and replicated a novel gene, ETFB, strongly associated with chronic AIC independently of age at tumor onset and related to anthracycline-mediated mitochondrial dysfunction. Although experimental verification and further studies in larger patient cohorts are required to confirm our finding, we demonstrated that exome array data analysis represents a valuable strategy to identify novel genes contributing to the susceptibility to chronic AIC. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/271330Test |
| DOI: | 10.17863/CAM.17690 |
| الإتاحة: | https://doi.org/10.17863/CAM.17690Test https://www.repository.cam.ac.uk/handle/1810/271330Test |
| رقم الانضمام: | edsbas.33923C23 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.17690 |
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