Oncotarget

Research Papers:

Vascular endothelium function among male carriers of BRCA 1&2 germline mutation

Guy Witberg, Eli Lev, Yaara Ber, Tzlil Tabachnik, Sivan Sela, Ira Belo, Dorit Leshem-Lev and David Margel _

PDF  |  Full Text  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2019; 10:5041-5051. https://doi.org/10.18632/oncotarget.27118

Metrics: PDF 152 views  |   Full Text 377 views  |   ?  


Abstract

Guy Witberg1,2,*, Eli Lev1,4,5,*, Yaara Ber3, Tzlil Tabachnik3, Sivan Sela3, Ira Belo3, Dorit Leshem-Lev1,2 and David Margel2,3

1 Department of Cardiology, Rabin Medical Center, Petach Tikva, Israel

2 The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

3 Department of Urology, Rabin Medical Center, Petach Tikva, Israel

4 Department of Cardiology, Assuta Ashdod University Hospital, Ashdod, Israel

5 Faculty of Medicine, Ben Gurion University, Be'er Sheva, Israel

* These authors contributed equally to this work

Correspondence to:

David Margel,email: sdmargel@gmail.com

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 27118