BRCA2 gene mutations and coagulation-associated biomarkers
Pedro Perez-Segura, José J Zamorano-León, Daniel Acosta
1Antonio López Farré, Medicine Department, School of Medicine, Plaza Ramón y Cajal. SN, Universidad Complutense de Madrid, Madrid 28040, Spain,
Thrombosis and Haemostasis
|October 9, 2015
Summary
BRCA2 gene mutations are linked to higher levels of blood clotting proteins, independent of breast cancer. This finding may explain the increased risk of dangerous blood clots in mutation carriers.
Area of Science:
- Genetics
- Oncology
- Hematology
Background:
- Thromboembolic events are a leading cause of death in cancer patients.
- The underlying mechanisms of this heightened risk are not fully understood.
- BRCA2 gene mutations are known risk factors for certain cancers.
Purpose of the Study:
- To investigate if BRCA2 gene mutations alter circulating thrombocoagulation biomarker levels.
- To determine if breast cancer development influences these biomarker changes in BRCA2 mutation carriers.
Main Methods:
- Analysis of plasma biomarkers in 25 women with BRCA2 mutations (12 with breast cancer, 13 without) and 13 non-mutant controls.
- Measurement of specific protein isotypes (fibrinogen gamma chain, haptoglobin, serotransferrin, C3/C5 convertase, vitamin D binding protein, alpha1-antitrypsin) and platelet factors (PF4, P-selectin).
Main Results:
- BRCA2 mutation carriers showed elevated levels of fibrinogen gamma chain, haptoglobin, serotransferrin, C3/C5 convertase, PF4, and P-selectin compared to controls.
- Decreased levels of vitamin D binding protein and alpha1-antitrypsin were observed in BRCA2 mutation carriers.
- Specific BRCA2 mutations (conserving RAD51 binding) correlated with higher alpha1-antitrypsin levels.
- Cancer-free BRCA2 carriers had different levels of vitamin D binding protein and alpha1-antitrypsin compared to those with breast cancer.
Conclusions:
- BRCA2 mutations are associated with altered plasma levels of proteins involved in thrombo-coagulation.
- These changes appear to be independent of breast cancer development.
- The findings suggest a potential link between BRCA2 mutations and an increased risk of blood clots.
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