Kim Yeong C, Soliman Amr S, Cui Jian, Ramadan Mohamed, Hablas Ahmed, Abouelhoda Mohamed, Hussien Nehal, Ahmed Ola, Zekri Abdel-Rahman Nabawy, Seifeldin Ibrahim A, Wang San Ming
Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
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.
遗传易感性会增加家族性乳腺癌的风险。最近的研究表明，家族性乳腺癌的遗传易感性可能存在种族特异性。然而，目前关于该疾病遗传易感性的知识主要来自西方人群。仅以这些现有信息作为判断非西方人群易感性的唯一参考是不够的，还可能导致误诊。需要努力收集非西方人群的遗传易感性信息。埃及人群在反映其不同种族起源方面具有高度的遗传变异，埃及家族性乳腺癌的发病率也高于许多其他人群。我们使用全外显子组测序技术，对五个埃及家族性乳腺癌家系的遗传易感性进行了研究。这五个家系中不存在BRCA1、BRCA2和其他经典乳腺癌易感基因的致病变异。将这些遗传变异与白种人家族性乳腺癌的变异进行比较后发现，埃及家系中的变异比白种人家系中的变异更加多样和异质。在单个家系中或不同家系之间共享的不同功能类别的基因中发现了多个有害变异。我们的研究表明，埃及乳腺癌家系的遗传易感性可能与其他疾病人群不同，并支持对当地疾病家系进行全面筛查，以确定埃及家族性乳腺癌的遗传易感性。
