Unique Features of Germline Variation in Five Egyptian Familial Breast Cancer Families Revealed by Exome Sequencing

PLoS One. 2017 Jan 11;12(1):e0167581. doi: 10.1371/journal.pone.0167581. eCollection 2017.


Genetic predisposition increases the risk of familial breast cancer. Recent studies indicate that genetic predisposition for familial breast cancer can be ethnic-specific. However, current knowledge of genetic predisposition for the disease is predominantly derived from Western populations. Using this existing information as the sole reference to judge the predisposition in non-Western populations is not adequate and can potentially lead to misdiagnosis. Efforts are required to collect genetic predisposition from non-Western populations. The Egyptian population has high genetic variations in reflecting its divergent ethnic origins, and incident rate of familial breast cancer in Egypt is also higher than the rate in many other populations. Using whole exome sequencing, we investigated genetic predisposition in five Egyptian familial breast cancer families. No pathogenic variants in BRCA1, BRCA2 and other classical breast cancer-predisposition genes were present in these five families. Comparison of the genetic variants with those in Caucasian familial breast cancer showed that variants in the Egyptian families were more variable and heterogeneous than the variants in Caucasian families. Multiple damaging variants in genes of different functional categories were identified either in a single family or shared between families. Our study demonstrates that genetic predisposition in Egyptian breast cancer families may differ from those in other disease populations, and supports a comprehensive screening of local disease families to determine the genetic predisposition in Egyptian familial breast cancer.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics*
  • Egypt
  • Exome*
  • Family
  • Female
  • Genetic Predisposition to Disease*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Male
  • Middle Aged


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human

Grants and funding

This study was supported by a pilot grant from the Fred & Pamela Buffett Cancer Center to Dr. San Ming Wang and Dr. Amr S. Soliman (http://www.unmc.edu/eppley/), a grant from the Eplley Cancer institute to Dr. San Ming Wang (http://www.unmc.edu/eppley/), and a grant from Science & Technology Development Fund in Egypt to Abdel-Rahman Nabawy Zekri (Grant number 5193). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.