title: Vascular endothelial growth factor A (VEGFA) gene polymorphisms have an impact on survival in a subgroup of indolent patients with chronic lymphocytic leukemia.
abstract: Vascular endothelial growth factor (VEGF)-mediated angiogenesis contributes to the pathogenesis of B-cell chronic lymphocytic leukaemia (CLL). We investigated the impact of VEGFA gene diversity on the clinical outcome of patients with this disease. A VEGFA haplotype conformed by positions rs699947 (-1540C>A), rs833061 (-460T>C) and rs2010963 (405C>G) and two additional single-nucleotide polymorphisms (SNPs), rs3025039 (936C>T) and rs25648 (1032C>T), were analysed in 239 patients at the time of their CLL diagnosis. Here, we showed that homozygosity for rs699947/rs833061/rs2010963 ACG haplotype (ACG+/+ genotype) correlated with a reduced survival in CLL patients (ACG+/+ vs other genotypes: HR = 2.3, p = 0.002; recessive model). In multivariate analysis, the ACG+/+ genotype was identified as a novel independent prognostic factor (HR = 2.1, p = 0.005). Moreover, ACG homozygosity subdivided patients with CLL with otherwise indolent parameters into prognostic subgroups with different outcomes. Specifically, patients carrying the ACG+/+ genotype with mutated IgVH, very low and low-risk cytogenetics, initial clinical stage, CD38 negative status or early age at diagnosis showed a shorter survival (ACG+/+ vs other genotypes: HR = 3.5, p = 0.035; HR = 3.4, p = 0.001; HR = 2.2, p = 0.035; HR = 3.4, p = 0.0001 and HR = 3.1, p = 0.009, respectively). In conclusion, VEGFA ACG+/+ genotype confers an adverse effect in overall survival in CLL patients with an indolent course of the disease. These observations support the biological and prognostic implications of VEGFA genetics in CLL.
authors: Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Carol
authors: C
authors: Lozano-Santos
authors: Group of Immunogenetics, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Jimena
authors: J
authors: Martinez-Velasquez
authors: Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Belen
authors: B
authors: Fernandez-Cuevas
authors: Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Natividad
authors: N
authors: Polo
authors: Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Belen
authors: B
authors: Navarro
authors: Department of Statistics, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Isabel
authors: I
authors: Millan
authors: Group of Oncology, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Jose Miguel
authors: JM
authors: Garcia
authors: Department of Hematology, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors: Rosa
authors: R
authors: Collado
authors: Department of Hematology, Hospital Severo Ochoa de Madrid, Madrid, Spain.
authors: Pedro
authors: P
authors: Sanchez-Godoy
authors: Department of Hematology, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors: Felix
authors: F
authors: Carbonell
authors: Department of Hematology, Hospital Universitario Ramón y Cajal de Madrid, Madrid, Spain.
authors: Jose Antonio
authors: JA
authors: Garcia-Vela
authors: Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Jose Antonio
authors: JA
authors: Garcia-Marco
authors: Group of Immunogenetics, Hospital Universitario Puerta de Hierro Majadahonda & Instituto de Investigación Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain.
authors: Natalia
authors: N
authors: Gomez-Lozano
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A