title: Unique Features of Germline Variation in Five Egyptian Familial Breast Cancer Families Revealed by Exome Sequencing.
abstract: 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.
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Yeong C
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Amr S
authors.initials: AS
authors.lastname: Soliman
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.affiliation: Gharbiah Cancer Society, Gharbiah Population-based Registry, Tanta, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ramadan
authors.affiliation: Gharbiah Cancer Society, Gharbiah Population-based Registry, Tanta, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hablas
authors.affiliation: Faculty of Engineering, Cairo University, Giza, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abouelhoda
authors.affiliation: Egypt National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: Nehal
authors.initials: N
authors.lastname: Hussien
authors.affiliation: Egypt National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: Ola
authors.initials: O
authors.lastname: Ahmed
authors.affiliation: Egypt National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: Abdel-Rahman Nabawy
authors.initials: AN
authors.lastname: Zekri
authors.affiliation: Gharbiah Cancer Society, Gharbiah Population-based Registry, Tanta, Egypt.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Seifeldin
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: San Ming
authors.identifier: 0000-0002-2172-1320
authors.initials: SM
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004534:Egypt; D059472:Exome; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human