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Keywords: BRCA; DNA repair; endothelial progenitor cells; vascular endothelium damage; cardiovascular system
Received: January 31, 2019
Accepted: June 29, 2019
Published: August 20, 2019
ABSTRACT
Background: Breast cancer susceptibility genes 1&2 (BRCA1&2) mutations hinder DNA-repair. Germline mutations in these genes are known to cause cancer; however, they may have other consequences. In this study we evaluated for the first time, the effect of the BRCA mutations on the vascular endothelium of young healthy males.
Results: The study included 82 participants (53 BRCA mutation positive-carriers and 29 negative-carriers). Subjects mean age was 40. There were no significant differences in the baseline characteristics of the two groups. BRCA-carriers had significantly higher levels of EPCs (fraction of CD34+/VEGF or CD133+/VEGF positive-cells) compared to non-carriers of the mutation (median 6.78[1.96,14.48]% vs. 1.46[0.65,6.18]%, p < 0.001, and median 7.17[1.70,16.69]% vs. 1.54[0.85,5.10]%, p < 0.001, respectively). This difference remained consistent after multivariate adjustment. We did not identify differences in endothelial function, endothelial damage markers and EPCs activity between the two groups.
Methods: This was a prospective cohort study to test the association between BRCA status and possible endothelial alterations. The Study population included males, 18-50 years, with no cardiovascular morbidity, who were referred for BRCA screening. We tested the endothelial system by: Endothelial progenitor cells (EPC) production, endothelial function (EndoPAT2000), endothelial damage and related hormonal levels. We stratified the cohort by germline BRCA status and compared measurements between BRCA mutation positive- and negative-carriers.
Conclusions: Male BRCA1&2 mutation positive-carriers had increased level of EPCs which may reflect a subclinical accumulative endothelial damage. These novel findings suggest that the effect of mutations in BRCA is not limited to increased cancer risk, but may affect the cardiovascular system.
