Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium

Sanchez-Maldonado JM, Campa D, Springer J, Badiola J, Niazi Y, Moniz-Diez A, Hernandez-Mohedo F, Gonzalez-Sierra PA, Ter Horst R, Macauda A, Brezina S, Cunha C, Lackner M, Lopez-Nevot MA, Fianchi L, Pagano L, Lopez-Fernandez E, Potenza L, Luppi M, Moratalla L, Rodriguez-Sevilla JJ, Fonseca JE, Tormo M, Solano C, Clavero E, Romero A, Li Y, Lass-Florl C, Einsele H, Vazquez L, Loeffler J, Hemminki K, Carvalho A, Netea MG, Gsur A, Dumontet C, Canzian F, Forsti A, Jurado M, Sainz J (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 10

Article Number: 75

Journal Issue: 7

DOI: 10.1038/s41408-020-00341-y

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.

Involved external institutions

Centro Hospitalar Universitário Lisboa Norte (CHULN) Portugal (PT) University of València / Universitat de València Spain (ES) Universidad de Granada Spain (ES) University of Pisa / Università di Pisa (UniPi) Italy (IT) Universitätsklinikum Würzburg Germany (DE) Hospital Universitario Virgen de las Nieves Spain (ES) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Radboud University Nijmegen Netherlands (NL) Medizinische Universität Wien Austria (AT) Universidade do Minho Portugal (PT) Medizinische Universität Innsbruck Austria (AT) Catholic University of the Sacred Heart / Università Cattolica del Sacro Cuore Italy (IT) Università degli Studi di Modena e Reggio Emilia (UNIMORE) Italy (IT) Hospital del Mar Spain (ES) University of Salamanca / Universidad de Salamanca Spain (ES) Université Claude Bernard Lyon 1 (UCB) France (FR)

How to cite

APA:

Sanchez-Maldonado, J.M., Campa, D., Springer, J., Badiola, J., Niazi, Y., Moniz-Diez, A.,... Sainz, J. (2020). Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium. Blood Cancer Journal, 10(7). https://doi.org/10.1038/s41408-020-00341-y

MLA:

Sanchez-Maldonado, J. M., et al. "Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium." Blood Cancer Journal 10.7 (2020).

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