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

JM. Sánchez-Maldonado, D. Campa, J. Springer, J. Badiola, Y. Niazi, A. Moñiz-Díez, F. Hernández-Mohedo, P. González-Sierra, R. Ter Horst, A. Macauda, S. Brezina, C. Cunha, M. Lackner, MA. López-Nevot, L. Fianchi, L. Pagano, E. López-Fernández, L....

. 2020 ; 10 (7) : 75. [pub] 20200716

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21012357

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.

Centre for Individualised Infection Medicine Hannover Germany

Department for Immunology and Metabolism Life and Medical Sciences Institute University of Bonn 53115 Bonn Germany

Department of Genetics University of Pisa Pisa Italy

Department of Internal Medicine and Radboud Center for Infectious Diseases Radboud University Nijmegen Medical Center Nijmegen The Netherlands

Department of Medical and Surgical Sciences University of Modena and Reggio Emilia AOU Policlinico Modena Italy

Department of Medicine University of Granada Granada Spain

Division of Cancer Epidemiology German Cancer Research Centre 69120 Heidelberg Germany

Division of Hygiene and Medical Microbiology Medical University of Innsbruck Innsbruck Austria

Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany

Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague 30605 Pilsen Czech Republic

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

Genomic Oncology Area GENYO Centre for Genomics and Oncological Research Pfizer University of Granada Andalusian Regional Government PTS Granada Granada Spain

Hematology department Hospital Clinico Universitario INCLIVA University of Valencia Valencia Spain

Hematology department Hospital del Mar Barcelona Spain

Hematology department University Hospital of Salamanca Salamanca Spain

Hematology department Virgen de las Nieves University Hospital Granada Spain

Hopp Children's Cancer Center Heidelberg Germany

ICVS 3B's PT Government Associate Laboratory Braga Guimarães Guimarães Portugal

Immunology department Virgen de las Nieves University Hospital Granada Spain

Institute of Cancer Research Department of Medicine 1 Medical University of Vienna Vienna Austria

Instituto de Investigación Biosanitaria de Granada Complejo Hospitales Universitarios de Granada Universidad de Granada Granada Spain

Istituto di Ematologia Università Cattolica del S Cuore Rome Italy

Life and Health Sciences Research Institute School of Medicine University of Minho Braga Portugal

Rheumatology and Metabolic Bone Diseases department Hospital de Santa Maria CHLN Lisbon Portugal

Rheumatology Research Unit Instituto de Medicina Molecular Faculty of Medicine University of Lisbon Lisbon Academic Medical Center Lisbon Portugal

Universitätsklinikum Würzburg Medizinische Klinik 2 Würzburg Germany

Université Claude Bernard Lyon 1 Lyon France

References provided by Crossref.org

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$a Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium / $c JM. Sánchez-Maldonado, D. Campa, J. Springer, J. Badiola, Y. Niazi, A. Moñiz-Díez, F. Hernández-Mohedo, P. González-Sierra, R. Ter Horst, A. Macauda, S. Brezina, C. Cunha, M. Lackner, MA. López-Nevot, L. Fianchi, L. Pagano, E. López-Fernández, L. Potenza, M. Luppi, L. Moratalla, JJ. Rodríguez-Sevilla, JE. Fonseca, M. Tormo, C. Solano, E. Clavero, A. Romero, Y. Li, C. Lass-Flörl, H. Einsele, L. Vazquez, J. Loeffler, K. Hemminki, A. Carvalho, MG. Netea, A. Gsur, C. Dumontet, F. Canzian, A. Försti, M. Jurado, J. Sainz
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$a 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.
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