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BRCA2 gene mutations and coagulation-associated biomarkers

Perez-Segura, Pedro; Zamorano-León, José J.; Acosta, Daniel; Santos-Sancho, Juana María; Modrego, Javier; Caldés, Trinidad; De La Hoya, Miguel; Díaz-Rubio, Eduardo; Díaz-Millán, Isabel and De Las Heras, Natalia, et al. (2016) In Thrombosis and Haemostasis 115(2). p.415-423
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 nonmutant 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... (More)

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 nonmutant 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.

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type
Contribution to journal
publication status
published
subject
keywords
BRCA2 mutations, Breast cancer, Coagulation, Thrombosis
in
Thrombosis and Haemostasis
volume
115
issue
2
pages
9 pages
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • Scopus:84957558016
ISSN
0340-6245
DOI
10.1160/TH15-06-0520
language
English
LU publication?
yes
id
9f27bd57-f1be-48d5-b205-902744bab972
date added to LUP
2016-07-19 08:58:13
date last changed
2016-10-13 05:11:49
@misc{9f27bd57-f1be-48d5-b205-902744bab972,
  abstract     = {<p>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 nonmutant 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.</p>},
  author       = {Perez-Segura, Pedro and Zamorano-León, José J. and Acosta, Daniel and Santos-Sancho, Juana María and Modrego, Javier and Caldés, Trinidad and De La Hoya, Miguel and Díaz-Rubio, Eduardo and Díaz-Millán, Isabel and De Las Heras, Natalia and Zalba, Luis Alfonso Rico and Lahera, Vicente and Melander, Olle and Farré, Antonio López},
  issn         = {0340-6245},
  keyword      = {BRCA2 mutations,Breast cancer,Coagulation,Thrombosis},
  language     = {eng},
  number       = {2},
  pages        = {415--423},
  publisher    = {ARRAY(0xdcbc018)},
  series       = {Thrombosis and Haemostasis},
  title        = {BRCA2 gene mutations and coagulation-associated biomarkers},
  url          = {http://dx.doi.org/10.1160/TH15-06-0520},
  volume       = {115},
  year         = {2016},
}