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

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• dc.contributor.author Bruzzoni-Giovanelli, Heribertoca
• dc.contributor.author González Ruiz, Juan Ramónca
• dc.contributor.author Sigaux, Françoisca
• dc.contributor.author Villoutreix, Bruno O.ca
• dc.contributor.author Cayuela, Jean Michelca
• dc.contributor.author Guilho, Joëlleca
• dc.contributor.author Preudhomme, Claudeca
• dc.contributor.author Guilhot, Françoisca
• dc.contributor.author Poyet, Jean-Lucca
• dc.contributor.author Rousselot, Philippeca
• dc.date.accessioned 2016-01-26T12:23:16Z
• dc.date.available 2016-01-26T12:23:16Z
• dc.date.issued 2015
• dc.description.abstract 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.ca
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Bruzzoni-Giovanelli H, González JR, Sigaux F, Villoutreix BO, Cayuela JM, Guilhot J. et al. Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia. Oncotarget. 2015 Nov 3;6(34):36269-77. doi: 10.18632/oncotarget.5915.ca
• dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.5915
• dc.identifier.issn 1949-2553
• dc.identifier.uri http://hdl.handle.net/10230/25659
• dc.language.iso engca
• dc.publisher Impact Journalsca
• dc.relation.ispartof Oncotarget. 2015 Nov 3;6(34):36269-77
• dc.rights This 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.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/3.0/ca
• dc.subject.other Leucèmia mieloide aguda -- Aspectes genèticsca
• dc.subject.other Polimorfisme genètic
• dc.title Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia.ca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca