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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Wheeler, Heather E | es-ES |
dc.contributor.author | González-Neira, Anna | es-ES |
dc.contributor.author | Pita, Guillermo | es-ES |
dc.contributor.author | de la Torre Montero, Julio César | es-ES |
dc.contributor.author | Alonso, Rosario | es-ES |
dc.contributor.author | López-Fernández, Luis | es-ES |
dc.contributor.author | Alba, Emilio | es-ES |
dc.contributor.author | Martín, Miguel | es-ES |
dc.contributor.author | Dolan, M Eileen | es-ES |
dc.date.accessioned | 2016-04-20T20:06:56Z | - |
dc.date.available | 2016-04-20T20:06:56Z | - |
dc.date.issued | 01/05/2014 | es_ES |
dc.identifier.issn | 1744-6872 | es_ES |
dc.identifier.uri | http://hdl.handle.net/11531/7228 | - |
dc.description | Artículos en revistas | es_ES |
dc.description.abstract | . | es-ES |
dc.description.abstract | Objective A primary challenge in identifying replicable pharmacogenomic markers from clinical genome wide association study (GWAS) trials in oncology is the difficulty of performing a second large clinical trial with the same drugs and dosage regimen. We sought to overcome this challenge by incorporating GWAS results from cell-based studies using the same chemotherapy as a clinical cohort. Methods In this study, we test whether the overlap between genetic variants identified in a preclinical and clinical study of capecitabine is more than expected by chance. A GWAS of capecitabine-induced cytotoxicity was performed in 164 lymphoblastoid cell lines (LCLs) derived from the CEU HapMap population and compared to a GWAS of hand-foot syndrome (HFS), the most frequent capecitabine-induced adverse drug reaction (ADR), in Spanish breast and colorectal cancer patients (n=160) treated with capecitabine. Results We observed an overlap of 16 single nucleotide polymorphisms (SNPs) associated with capecitabine-induced cytotoxicity (P < 0.001) in LCLs and HFS (P < 0.05) in patients, which is a greater overlap than expected by chance (genotype-phenotype permutation empirical P = 0.015). Ten tag SNPs, which cover the overlap loci, were genotyped in a second patient cohort (n=85) and one of them, rs9936750, associated with capecitabine-induced HFS (P = 0.0076).Conclusions The enrichment results imply that cellular models of capecitabine-induced cytotoxicity may capture components of the underlying polygenic architecture of related toxicities in patients. | en-GB |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | en-GB | es_ES |
dc.rights | Creative Commons Reconocimiento-NoComercial-SinObraDerivada España | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | es_ES |
dc.source | Revista: Pharmacogenetics and Genomics, Periodo: 1, Volumen: 24, Número: 5, Página inicial: 231, Página final: 237 | es_ES |
dc.title | Identification of genetic variants associated with capecitabine-induced hand-foot syndrome through integration of patient and cell line genomic analyses. | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.description.version | info:eu-repo/semantics/publishedVersion | es_ES |
dc.rights.holder | es_ES | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.keywords | . | es-ES |
dc.keywords | capecitabine toxicity; genome-wide association; integrative modeling; hand-foot syndrome; lymphoblastoid cell lines | en-GB |
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