Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis.

Autor: Gonçalves AC; Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra-FMUC, Coimbra, Portugal.; Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal.; Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal., Alves R; Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra-FMUC, Coimbra, Portugal.; Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal.; Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal., Baldeiras I; Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal.; Department of Neurology, Laboratory of Neurochemistry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.; Faculty of Medicine, University of Coimbra-FMUC, Coimbra, Portugal., Cortesão E; Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra-FMUC, Coimbra, Portugal.; Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal.; Clinical Hematology Department, Centro Hospitalar e Universitário de Coimbra, EPE (CHUC, EPE), Coimbra, Portugal., Carda JP; Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra-FMUC, Coimbra, Portugal.; Clinical Hematology Department, Centro Hospitalar e Universitário de Coimbra, EPE (CHUC, EPE), Coimbra, Portugal., Branco CC; Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE, Ponta Delgada, São Miguel Island, Azores, Portugal.; Azores Genetics Research Group, Instituto Gulbenkian de Ciência, Oeiras, Portugal.; Faculty of Sciences, BioISI-Biosystems and Integrative Sciences Institute, University of Lisboa, Lisbon, Portugal., Oliveiros B; Laboratory for Biostatistics and Medical Informatics, FMUC, Coimbra, Portugal., Loureiro L; Department of Medicine, Hospital Distrital da Figueira da Foz, EPE (HDFF, EPE), Figueira da Foz, Portugal., Pereira A; Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal.; Department of Medicine, Hospital Distrital da Figueira da Foz, EPE (HDFF, EPE), Figueira da Foz, Portugal., Nascimento Costa JM; Department of Oncology, Centro Hospitalar e Universitário de Coimbra, EPE (CHUC, EPE), Coimbra, Portugal.; Faculty of Medicine, University Clinic of Oncology, University of Coimbra-FMUC, Coimbra, Portugal., Sarmento-Ribeiro AB; Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra-FMUC, Coimbra, Portugal.; Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), FMUC, Coimbra, Portugal.; Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Coimbra, Portugal.; Clinical Hematology Department, Centro Hospitalar e Universitário de Coimbra, EPE (CHUC, EPE), Coimbra, Portugal., Mota-Vieira L; Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE, Ponta Delgada, São Miguel Island, Azores, Portugal.; Azores Genetics Research Group, Instituto Gulbenkian de Ciência, Oeiras, Portugal.; Faculty of Sciences, BioISI-Biosystems and Integrative Sciences Institute, University of Lisboa, Lisbon, Portugal.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2017 Jan; Vol. 56 (1), pp. 130-148. Date of Electronic Publication: 2016 Mar 07.
DOI: 10.1002/mc.22478
Abstrakt: Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2'-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.
(© 2016 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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