Castillo Cecilia, Artagaveytia Nora, Brignoni Lucia, Laitman Yael, Camejo Natalia, Hernández Ana Laura, Krygier Gabriel, Cayota Alfonso, Delgado Lucia, Friedman Eitan
Servicio de Oncología Clínica, Hospital de Clínicas "Dr. Manuel Quintela", Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay.
Departamento Básico de Medicina, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Mol Genet Genomic Med. 2022 Jun;10(6):e1928. doi: 10.1002/mgg3.1928. Epub 2022 Mar 25.
In Ashkenazi Jews (AJ) three recurring pathogenic sequence variants (PSVs) are detected in ~2.5% of the general population in the BRCA1 (c.68_69del = 185delAG, c.5266dup = 5382insC), and BRCA2 (c.5946del = 6174delT). Population-based screening for these PSVs in AJ women is part of the health basket in Israel. To assess the feasibility and outcome of BRCA genotyping in the Jewish population of Uruguay, AJ in the greater Montevideo area were recruited using ethically approved protocol and without pretest counseling were genotyped for the three predominant AJ PSVs in the BRCA genes. Independently confirmed PSV carriers were counseled, and genetic testing was offered to additional family members. Overall, 327 participants were enrolled: 312 (95%) female, 261 (80%) had all four grandparents AJ, and 14 (4%) women were breast cancer survivors with a mean age ± standard deviation (SD) 50 ± 11.5 years. The BRCA1 c.68_69del PSV was detected in three cancer free participants (0.92%, CI 95% 0.31-2.6), all with a suggestive family history. No carriers of the other two recurrent PSVs were detected. Online oncogenetic counseling was provided for all carriers. In conclusion, the rate of the BRCA1 c.68_69del PSV was similar with the rate in other AJ communities. AJ population BRCA genotyping screens in Uruguay seem feasible and should be promoted.
在阿什肯纳兹犹太人（AJ）中，约2.5%的普通人群中检测到BRCA1基因（c.68_69del = 185delAG，c.5266dup = 5382insC）和BRCA2基因（c.5946del = 6174delT）的三种常见致病序列变异（PSV）。在以色列，针对AJ女性进行这些PSV的人群筛查是健康福利的一部分。为评估在乌拉圭犹太人群体中进行BRCA基因分型的可行性和结果，采用符合伦理规范的方案招募了蒙得维的亚大区的AJ人群，且未进行检测前咨询，对BRCA基因中三种主要的AJ PSV进行基因分型。对独立确认的PSV携带者进行了咨询，并为其他家庭成员提供了基因检测。总体而言，共招募了327名参与者：312名（95%）为女性，261名（80%）的四位祖父母均为AJ，14名（4%）女性是乳腺癌幸存者，平均年龄±标准差（SD）为50±11.5岁。在三名无癌参与者中检测到BRCA1基因的c.68_69del PSV（0.92%，95%置信区间0.31 - 2.6），所有携带者均有提示性家族史。未检测到其他两种常见PSV的携带者。为所有携带者提供了在线肿瘤遗传学咨询。总之，BRCA1基因c.68_69del PSV的发生率与其他AJ群体相似。乌拉圭AJ人群的BRCA基因分型筛查似乎可行，应予以推广。
