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dc.contributor.authorCaronia, Daniela
dc.contributor.authorPatiño-García, Ana
dc.contributor.authorPérez Martínez, Antonio 
dc.contributor.authorPita, Guillermo
dc.contributor.authorMoreno, Leticia Tais
dc.contributor.authorZalacaín Díez, Marta
dc.contributor.authorMolina, Blanca
dc.contributor.authorColmenero, Isabel
dc.contributor.authorSierrasesúmaga, Luis
dc.contributor.authorBenítez, Javier F.
dc.contributor.authorGonzález-Neira, Anna
dc.contributor.otherUAM. Departamento de Pediatríaes_ES
dc.date.accessioned2015-04-14T08:14:46Z
dc.date.available2015-04-14T08:14:46Z
dc.date.issued2011-10-07
dc.identifier.citationPlos One 6.10 (2011): e26091es_ES
dc.identifier.issn1932-6203 (online)es_ES
dc.identifier.urihttp://hdl.handle.net/10486/665062
dc.description.abstractBackground: Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response. Methodology/Principal Findings: In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs) and 2 Copy Number Variants (CNVs) in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1×10 -5), and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9×10 -5), rs1128503 and rs10276036 (r 2 = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9×10 -5). Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] ≤0.03). Conclusions: Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapyen_US
dc.description.sponsorshipThis work was supported by the AECC (Asociación Española contra el Cáncer), FIS (Fondo de Investigación Sanitaria-Instituto de Salud Carlos III) and the ‘‘Inocente Inocente’’ Foundationes_ES
dc.format.extent6 pag.es_ES
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPlos Oneen_US
dc.rights© 2011 Caronia et ales_ES
dc.subject.otherAntineoplastic Agentsen_US
dc.subject.otherBiological Transporten_US
dc.subject.otherChilden_US
dc.subject.otherOsteosarcomaen_US
dc.subject.otherPharmacogeneticsen_US
dc.subject.otherMultidrug Resistance-Associated Proteinsen_US
dc.titleEffect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: A pharmacogenetic studyen_US
dc.typearticleen
dc.subject.ecienciaMedicinaes_ES
dc.identifier.doi10.1371/journal.pone.0026091es_ES
dc.identifier.publicationfirstpagee26091es_ES
dc.identifier.publicationissue10es_ES
dc.identifier.publicationlastpagee26091es_ES
dc.identifier.publicationvolume6es_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.rights.ccReconocimientoes_ES
dc.rights.accessRightsopenAccesses_ES
dc.facultadUAMFacultad de Medicina


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