title: BRCA2 gene mutations and coagulation-associated biomarkers.
abstract: Thromboembolic events are the second cause of death in cancer patients, although the mechanisms underlying this increased thromboembolic risk remain unclear. The aims of this study were to examine whether BRCA2 gene mutations may modify the circulating levels of thrombocoagulation biomarkers and whether breast cancer development may influence changes in such circulating biomarkers. The study was performed in 25 women with mutations in the BRCA2 gene (n=12 breast cancer, n=13 breast cancer-free) and in 13 BRCA2 non-mutant controls. Results revealed that plasma levels of fibrinogen gamma chain isotypes 2 and 3, haptoglobin isotypes 4 and 5, serotransferrin isotypes 3 and 4 and convertase C3/C5 isotypes 4 and 5 were significantly higher in BRCA2 mutation carriers compared to controls. However, plasma levels of vitamin D binding protein isotype 1 and alpha1-antitrypsin isotypes 2, 3 and 4 were significantly decreased in BRCA2 mutation carriers compared to controls. Plasma expression of PF4 and P-selectin was significantly higher in BRCA2 mutations carriers than in controls. BRCA2 truncated mutations conserving a binding region for RAD51 were associated with increased plasma levels of alpha1-antitrypsin isotypes 3 and 4 with respect to women showing BRCA2 mutations that loss the binding RD51 region to BRCA2. Only plasma levels of vitamin D binding protein isotypes 1 and 3 were significantly reduced and alpha 1-antitrypsin isotype 1 was increased in cancer-free BRCA2 mutation carriers compared to BRCA2 mutation carriers with breast cancer. The presence of BRCA2 mutations is associated with increased plasma levels of thrombo-coagulating-related proteins, which are independent to breast cancer development.
authors.forename: Pedro
authors.initials: P
authors.lastname: Perez-Segura
authors.forename: José J
authors.initials: JJ
authors.lastname: Zamorano-León
authors.forename: Daniel
authors.initials: D
authors.lastname: Acosta
authors.forename: Juana María
authors.initials: JM
authors.lastname: Santos-Sancho
authors.forename: Javier
authors.initials: J
authors.lastname: Modrego
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Isabel
authors.initials: I
authors.lastname: Díaz-Millán
authors.forename: Natalia
authors.initials: N
authors.lastname: de Las Heras
authors.forename: Luis Alfonso
authors.initials: LA
authors.lastname: Rico Zalba
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: Antonio López Farré, Medicine Department, School of Medicine, Plaza Ramón y Cajal. SN, Universidad Complutense de Madrid, Madrid 28040, Spain, E-mail: ajlf@telefonica.net.
authors.forename: Antonio
authors.initials: A
authors.lastname: López Farré
mesh_terms: D000328:Adult; D024682:BRCA2 Protein / Q000235:genetics*; D001665:Binding Sites; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006242:Haptoglobins / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D019007:P-Selectin / Q000097:blood; D010978:Platelet Factor 4 / Q000097:blood; D051135:Rad51 Recombinase / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D015415:Biomarkers; D006242:Haptoglobins; D019007:P-Selectin; C546937:SELP protein, human; D014168:Transferrin; D000515:alpha 1-Antitrypsin; D010978:Platelet Factor 4; D005340:Fibrinogen; C495153:RAD51 protein, human; D051135:Rad51 Recombinase
keywords: BRCA2 mutations; breast cancer; coagulation; thrombosis