title: Associations of VEGF and VEGFR2 polymorphisms with increased risk and aggressiveness of multiple myeloma.
abstract: Angiogenesis has been highlighted as a critical component in the progression of multiple myeloma (MM), and vascular endothelial growth factor (VEGF) as well as its type 2 receptor (VEGFR2) are thought to play a major role in the process. Single nucleotide polymorphisms (SNPs) have been described in VEGF and VEGFR2 genes, with quantitative or qualitative changes in encoded VEGF and VEGFR2. The roles of VEGF -2578C/A, -1154G/A, and -634G/C as well as VEGFR2 -604T/C and +1192G/A SNPs in the risk and manifestations of MM are still unknown; therefore, this study aimed to clarify this issue. DNA from 192 patients and 209 controls were analyzed by real-time polymerase chain reaction for identification of genotypes. The frequencies of VEGF -2578CC, VEGF -2578CC plus VEGF -634GG, and VEGF -2578CC plus VEGF -1154GG plus VEGF -634GG genotypes were higher in patients than in controls. Carriers of the respective genotypes had a 1.89-, a 5.52-, and a 4.91-fold increased risk for MM than others. VEGF -2578CC plus VEGFR2 +1192GG, VEGF -2578CC plus VEGF -634GG plus VEGFR2 +1192GG, and VEGF -1154GG plus VEGF -634GG plus VEGFR2 -604TT combined genotypes were more common in patients than in controls. Carriers of the respective genotypes had a 2.56-, a 10.97-, and a 14.10-fold increased risk for MM than others. An excess of VEGFR2 -604TT genotype was also seen in patients with stage II or III tumors when compared with those with stage I tumors. Our data suggest, for the first time, that inherited abnormalities in VEGF and VEGFR2 pathways influence the risk and aggressiveness of MM.
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Angelo Borsarelli Carvalho
authors.initials: AB
authors.lastname: Brito
authors.forename: Gustavo Jacob
authors.initials: GJ
authors.lastname: Lourenço
authors.forename: Gislaine Borba
authors.initials: GB
authors.lastname: Oliveira
authors.forename: Cármino Antônio
authors.initials: CA
authors.lastname: De Souza
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.forename: Carmen Silvia Passos
authors.initials: CS
authors.lastname: Lima
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000502:physiology
chemical_list: D020121:5' Untranslated Regions; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2