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

Autor: Sánchez-Maldonado JM; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Granada, Spain.; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., Campa D; Department of Genetics, University of Pisa, Pisa, Italy., Springer J; Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany., Badiola J; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., Niazi Y; Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany., Moñiz-Díez A; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Granada, Spain.; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., Hernández-Mohedo F; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., González-Sierra P; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., Ter Horst R; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands., Macauda A; Department of Genetics, University of Pisa, Pisa, Italy.; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany., Brezina S; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Cunha C; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Guimarães, Portugal., Lackner M; Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., López-Nevot MA; Immunology department, Virgen de las Nieves University Hospital, Granada, Spain., Fianchi L; Istituto di Ematologia, Università Cattolica del S. Cuore, Rome, Italy., Pagano L; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, Modena, Italy., López-Fernández E; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., Potenza L; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, Modena, Italy., Luppi M; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, Modena, Italy., Moratalla L; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., Rodríguez-Sevilla JJ; Hematology department, Hospital del Mar, Barcelona, Spain., Fonseca JE; 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., Tormo M; Hematology department, Hospital Clinico Universitario-INCLIVA, University of Valencia, Valencia, Spain., Solano C; Hematology department, Hospital Clinico Universitario-INCLIVA, University of Valencia, Valencia, Spain., Clavero E; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain., Romero A; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain., Li Y; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.; Centre for Individualised Infection Medicine (CiiM) & TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany., Lass-Flörl C; Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Einsele H; Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany., Vazquez L; Hematology department, University Hospital of Salamanca, Salamanca, Spain., Loeffler J; Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany., Hemminki K; Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), 69120, Heidelberg, Germany.; Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605, Pilsen, Czech Republic., Carvalho A; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Guimarães, Portugal., Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.; Department for Immunology & Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115, Bonn, Germany., Gsur A; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Dumontet C; Université Claude Bernard Lyon I, Lyon, France., Canzian F; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany., Försti A; Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany., Jurado M; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Granada, Spain.; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain., Sainz J; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Granada, Spain. juan.sainz@genyo.es.; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain. juan.sainz@genyo.es.; Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. juan.sainz@genyo.es.; Department of Medicine, University of Granada, Granada, Spain. juan.sainz@genyo.es.
Jazyk: angličtina
Zdroj: Blood cancer journal [Blood Cancer J] 2020 Jul 16; Vol. 10 (7), pp. 75. Date of Electronic Publication: 2020 Jul 16.
DOI: 10.1038/s41408-020-00341-y
Abstrakt: 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 IL13 rs1295686A/A genotype had an increased risk of AML (P Corr  = 0.0144) whereas carriers of the VEGFA rs25648T allele had a decreased risk of developing the disease (P Corr  = 0.00086). In addition, we found an association of the IL8 rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (P Corr  = 0.072). Functional experiments suggested that the effect of the IL13 rs1295686 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 IL8 rs2227307 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.
Databáze: MEDLINE
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