Thromb Haemost 2016; 115(02): 415-423
DOI: 10.1160/th15-06-0520
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

BRCA2 gene mutations and coagulation-associated biomarkers

Pedro Perez-Segura*
1   Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
,
José J Zamorano-León*
2   Instituto Investigaciones Sanitarias, Hospital Clínico San Carlos, Madrid. Spain
,
Daniel Acosta
1   Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
,
Juana María Santos-Sancho
3   School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
,
Javier Modrego
2   Instituto Investigaciones Sanitarias, Hospital Clínico San Carlos, Madrid. Spain
,
Trinidad Caldés
1   Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
,
Miguel de la Hoya
1   Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
,
Eduardo Díaz-Rubio
1   Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
,
Isabel Díaz-Millán
1   Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
,
Natalia de las Heras
3   School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
,
Luis Alfonso Rico Zalba
4   Fundación Jiménez Díaz, Madrid, Spain
,
Vicente Lahera
3   School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
,
Olle Melander
5   Department of Clinical Sciences, Lund University, Malmö, Sweden
,
Antonio López Farré
3   School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
› Author Affiliations

Financial support: This work has been supported by a grant from Oncology Spanish Society, Fondos de Investigaciones de la Seguridad Social [Redes temáticas de Investigación Cooperativa (RETICs) RD12/0042/0040, RD12/0042/0033 and RD06/0020/0021], Fondo Europeo de Desarrollo Regional (Fondos FEDER).
Further Information

Publication History

Received: 30 June 2015

Accepted after major revision: 10 September 2015

Publication Date:
22 November 2017 (online)

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Summary

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.

* These authors contributed equally to the manuscript.