دورية أكاديمية
Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer.
| العنوان: | Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer. |
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| المؤلفون: | Ruiz-Pinto, Sara, Pita, Guillermo, Patiño-García, Ana, Alonso, Javier, Pérez-Martínez, Antonio, Cartón, Antonio J, Gutiérrez-Larraya, Federico, Alonso, María R, Barnes, Daniel R, Dennis, Joe, Michailidou, Kyriaki, Gómez-Santos, Carmen, Thompson, Deborah J, Easton, Douglas F, Benítez, Javier, González-Neira, Anna |
| بيانات النشر: | Wolters Kluwer //dx.doi.org/10.1097/fpc.0000000000000309 Pharmacogenetics and Genomics |
| سنة النشر: | 2017 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Adolescent, Anthracyclines, Antineoplastic Agents, Child, Preschool, Exome, Female, Genetic Predisposition to Disease, Heart, Humans, Infant, Leukemia, Male, Osteosarcoma, Receptors, G-Protein-Coupled, Sarcoma, Ewing |
| الوصف: | OBJECTIVES: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. PATIENTS AND METHODS: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. RESULTS: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C>T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. CONCLUSION: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients. ; This work was supported by the Spanish Association against Cancer (AECC: Asociación Española contra el Cáncer). Human Genotyping lab is a member of CeGen, PRB2-ISCIII and is supported by grant PT13/0001, of the PE I+D+i 2013-2016, funded by ISCIII and FEDER (Fondo Europeo de Desarrollo Regional). Sara Ruiz-Pinto is a predoctoral fellow supported by the Severo Ochoa Excellence Programme (Project SEV-2011-0191). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/274616Test |
| DOI: | 10.17863/CAM.21759 |
| الإتاحة: | https://doi.org/10.17863/CAM.21759Test https://www.repository.cam.ac.uk/handle/1810/274616Test |
| رقم الانضمام: | edsbas.D9D2C94D |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.21759 |
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