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Functional FLT1 genetic variation is a prognostic factor for recurrence in stage I-III non-small cell lung cancer.

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Functional FLT1 genetic variation is a prognostic factor for recurrence in stage I-III non-small cell lung cancer.

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dc.contributor.author Glubb, Dylan M es_ES
dc.contributor.author Pare-Brunet, Laia es_ES
dc.contributor.author Jantus Lewintre, Eloisa es_ES
dc.contributor.author Jiang, Chen es_ES
dc.contributor.author Crona, Daniel es_ES
dc.contributor.author Etheridge, Amy S. es_ES
dc.contributor.author Mirza, Osman es_ES
dc.contributor.author Zhang, Wei es_ES
dc.contributor.author Seiser, Eric L. es_ES
dc.contributor.author Rzyman, Witold es_ES
dc.contributor.author Jassem, Jacek es_ES
dc.contributor.author Auman, Todd es_ES
dc.contributor.author Hirsch, Fred R es_ES
dc.contributor.author Owzar, Kouros es_ES
dc.contributor.author Camps, Carlos es_ES
dc.contributor.author Dziadziuszko, Rafal es_ES
dc.contributor.author Innocenti, Federico es_ES
dc.date.accessioned 2017-01-27T13:07:14Z
dc.date.available 2017-01-27T13:07:14Z
dc.date.issued 2015-07
dc.identifier.issn 1556-0864
dc.identifier.uri http://hdl.handle.net/10251/77411
dc.description Acceso abierto en: http://dx.doi.org/10.1097/JTO.0000000000000549 es_ES
dc.description.abstract Background: We propose that single-nucleotide polymorphisms (SNPs) in genes of the vascular endothelial growth factor pathway of angiogenesis will associate with survival in non-small-cell lung cancer (NSCLC) patients. Methods: Fifty-three SNPs in vascular endothelial growth factor-pathway genes were genotyped in 150 European stage I-III NSCLC patients and tested for associations with patient survival. Replication was performed in an independent cohort of 142 European stage I-III patients. Reporter gene assays were used to assess the effects of SNPs on transcriptional activity. Results: In the initial cohort, five SNPs associated (q < 0.05) with relapse-free survival (RFS). The minor alleles of intronic FLT1 SNPs, rs7996030 and rs9582036, associated with reduced RFS (hazard ratio [HR] = 1.67 [95% confidence interval, CI, 1.22-2.29] and HR = 1.51 [95% CI, 1.14-2.01], respectively) and reduced transcriptional activity. The minor alleles of intronic KRAS SNPs, rs12813551 and rs10505980, associated with increased RFS (HR = 0.64 [0.46-0.87] and HR = 0.64 [0.47-0.87], respectively), and the minor allelic variant of rs12813551 also reduced transcriptional activity. Lastly, the minor allele of the intronic KRAS SNP rs10842513 associated with reduced RFS (HR = 1.65 [95% CI, 1.16-2.37]). Analysis of the functional variants suggests they are located in transcriptional enhancer elements. The negative effect of rs9582036 on RFS was confirmed in the replication cohort (HR = 1.69 [0.99-2.89], p = 0.028), and the association was significant in pooled analysis of both cohorts (HR = 1.67 [1.21-2.30], p = 0.0001). Conclusions: The functional FLT1 variant rs9582036 is a prognostic determinant of recurrence in stage I-III NSCLC. Its predictive value should be tested in the adjuvant setting of stage I-III NSCLC. es_ES
dc.language Inglés es_ES
dc.publisher Lippincott, Williams & Wilkins es_ES
dc.relation.ispartof Journal of Thoracic Oncology es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Non-small cell lung cancer es_ES
dc.subject SNPs es_ES
dc.subject VEGF pathway es_ES
dc.subject FLT1 es_ES
dc.subject Enhancer es_ES
dc.subject.classification MICROBIOLOGIA es_ES
dc.title Functional FLT1 genetic variation is a prognostic factor for recurrence in stage I-III non-small cell lung cancer. es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1097/JTO.0000000000000549
dc.rights.accessRights Cerrado es_ES
dc.contributor.affiliation Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural - Escola Tècnica Superior d'Enginyeria Agronòmica i del Medi Natural es_ES
dc.description.bibliographicCitation Glubb, DM.; Pare-Brunet, L.; Jantus Lewintre, E.; Jiang, C.; Crona, D.; Etheridge, AS.; Mirza, O.... (2015). Functional FLT1 genetic variation is a prognostic factor for recurrence in stage I-III non-small cell lung cancer. Journal of Thoracic Oncology. 10(7):1067-1075. doi:10.1097/JTO.0000000000000549 es_ES
dc.description.accrualMethod Senia es_ES
dc.relation.publisherversion https://dx.doi.org/10.1097/JTO.0000000000000549 es_ES
dc.description.upvformatpinicio 1067 es_ES
dc.description.upvformatpfin 1075 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 10 es_ES
dc.description.issue 7 es_ES
dc.relation.senia 292545 es_ES


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