Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.

Little is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. S...

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Autores: Bruzzoni-Giovanelli, Heriberto, González Ruiz, Juan Ramón, Sigaux, François, Villoutreix, Bruno O., Cayuela, Jean Michel, Guilho, Joëlle, Preudhomme, Claude, Guilhot, François, Poyet, Jean-Luc, Rousselot, Philippe
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/25659
Acceso en línea:http://hdl.handle.net/10230/25659
http://dx.doi.org/10.18632/oncotarget.5915
Access Level:acceso abierto
Palabra clave:Leucèmia mieloide aguda -- Aspectes genètics
Polimorfisme genètic
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spelling Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.Bruzzoni-Giovanelli, HeribertoGonzález Ruiz, Juan RamónSigaux, FrançoisVilloutreix, Bruno O.Cayuela, Jean MichelGuilho, JoëllePreudhomme, ClaudeGuilhot, FrançoisPoyet, Jean-LucRousselot, PhilippeLeucèmia mieloide aguda -- Aspectes genèticsPolimorfisme genèticLittle is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. Single SNP association analysis identified 139 SNPs that passed multiple comparisons (1% false discovery rate). The HDAC9, AVEN, SEMA3C, IKBKB, GSTA3, RIPK1 and FGF2 genes were each represented by three SNPs, the PSM family by four SNPs and the SLC15A1 gene by six. Haplotype analysis showed that certain combinations of rare alleles of these genes increased the risk of developing CML by more than two or three-fold. A classification tree model identified five SNPs belonging to the genes PSMB10, TNFRSF10D, PSMB2, PPARD and CYP26B1, which were associated with CML predisposition. A CML-risk-allele score was created using these five SNPs. This score was accurate for discriminating CML status (AUC: 0.61, 95%CI: 0.58-0.64). Interestingly, the score was associated with age at diagnosis and the average number of risk alleles was significantly higher in younger patients. The risk-allele score showed the same distribution in the general population (HapMap CEU samples) as in our control individuals and was associated with differential gene expression patterns of two genes (VAPA and TDRKH). In conclusion, we describe haplotypes and a genetic score that are significantly associated with a predisposition to develop CML. The SNPs identified will also serve to drive fundamental research on the putative role of these genes in CML development.This work was supported by INSERM (Pharmacogenetic-REPAC Network), by the Grant U03S03 from the ECOS-Sud program (France-Uruguay), a Grant from the Association Jean Bernard, France and a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique (PHRC 2011, 11N28), SPIRIT ClinicalTrials.gov Identifier: NCT00219739.Impact Journals201620162015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/25659http://dx.doi.org/10.18632/oncotarget.5915reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésOncotarget. 2015 Nov 3;6(34):36269-77This is an open-access article distributed under the terms of the http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/256592026-06-12T07:21:37Z
dc.title.none.fl_str_mv Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
title Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
spellingShingle Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
Bruzzoni-Giovanelli, Heriberto
Leucèmia mieloide aguda -- Aspectes genètics
Polimorfisme genètic
title_short Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
title_full Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
title_fullStr Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
title_full_unstemmed Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
title_sort Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.
dc.creator.none.fl_str_mv Bruzzoni-Giovanelli, Heriberto
González Ruiz, Juan Ramón
Sigaux, François
Villoutreix, Bruno O.
Cayuela, Jean Michel
Guilho, Joëlle
Preudhomme, Claude
Guilhot, François
Poyet, Jean-Luc
Rousselot, Philippe
author Bruzzoni-Giovanelli, Heriberto
author_facet Bruzzoni-Giovanelli, Heriberto
González Ruiz, Juan Ramón
Sigaux, François
Villoutreix, Bruno O.
Cayuela, Jean Michel
Guilho, Joëlle
Preudhomme, Claude
Guilhot, François
Poyet, Jean-Luc
Rousselot, Philippe
author_role author
author2 González Ruiz, Juan Ramón
Sigaux, François
Villoutreix, Bruno O.
Cayuela, Jean Michel
Guilho, Joëlle
Preudhomme, Claude
Guilhot, François
Poyet, Jean-Luc
Rousselot, Philippe
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Leucèmia mieloide aguda -- Aspectes genètics
Polimorfisme genètic
topic Leucèmia mieloide aguda -- Aspectes genètics
Polimorfisme genètic
description Little is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. Single SNP association analysis identified 139 SNPs that passed multiple comparisons (1% false discovery rate). The HDAC9, AVEN, SEMA3C, IKBKB, GSTA3, RIPK1 and FGF2 genes were each represented by three SNPs, the PSM family by four SNPs and the SLC15A1 gene by six. Haplotype analysis showed that certain combinations of rare alleles of these genes increased the risk of developing CML by more than two or three-fold. A classification tree model identified five SNPs belonging to the genes PSMB10, TNFRSF10D, PSMB2, PPARD and CYP26B1, which were associated with CML predisposition. A CML-risk-allele score was created using these five SNPs. This score was accurate for discriminating CML status (AUC: 0.61, 95%CI: 0.58-0.64). Interestingly, the score was associated with age at diagnosis and the average number of risk alleles was significantly higher in younger patients. The risk-allele score showed the same distribution in the general population (HapMap CEU samples) as in our control individuals and was associated with differential gene expression patterns of two genes (VAPA and TDRKH). In conclusion, we describe haplotypes and a genetic score that are significantly associated with a predisposition to develop CML. The SNPs identified will also serve to drive fundamental research on the putative role of these genes in CML development.
publishDate 2015
dc.date.none.fl_str_mv 2015
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/25659
http://dx.doi.org/10.18632/oncotarget.5915
url http://hdl.handle.net/10230/25659
http://dx.doi.org/10.18632/oncotarget.5915
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Oncotarget. 2015 Nov 3;6(34):36269-77
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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