Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium
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- dc.contributor.author Sánchez-Maldonado, J.M.
- dc.contributor.author Rodríguez-Sevilla, Juan José
- dc.contributor.author Sainz, J.
- dc.date.accessioned 2020-09-09T06:57:01Z
- dc.date.available 2020-09-09T06:57:01Z
- dc.date.issued 2020
- dc.description.abstract The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.
- dc.format.mimetype application/pdf
- dc.identifier.citation Sánchez-Maldonado JM, Campa D, Springer J, Badiola J, Niazi Y, Moñiz-Díez A. et al. Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium. Blood Cancer J. 2020 Jul 16; 10(7):75. DOI: 10.1038/s41408-020-00341-y
- dc.identifier.doi http://dx.doi.org/10.1038/s41408-020-00341-y
- dc.identifier.issn 2044-5385
- dc.identifier.uri http://hdl.handle.net/10230/45275
- dc.language.iso eng
- dc.publisher Nature Research
- dc.rights © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Risk factors
- dc.subject.keyword Genetics research
- dc.subject.other Leucèmia mieloide aguda -- Aspectes genètics
- dc.title Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion