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Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants
European Journal of Human Genetics ( IF 3.7 ) Pub Date : 2020-11-23 , DOI: 10.1038/s41431-020-00760-2
Liis Leitsalu 1 , Marili Palover 1, 2 , Timo Tõnis Sikka 1, 2 , Anu Reigo 1 , Mart Kals 1, 3 , Kalle Pärn 1, 3 , Tiit Nikopensius 1 , Tõnu Esko 1 , Andres Metspalu 1, 2 , Peeter Padrik 4, 5 , Neeme Tõnisson 1, 6
Affiliation  

Genotype-first approach allows to systematically identify carriers of pathogenic variants in BRCA1/2 genes conferring a high risk of familial breast and ovarian cancer. Participants of the Estonian biobank have expressed support for the disclosure of clinically significant findings. With an Estonian biobank cohort, we applied a genotype-first approach, contacted carriers, and offered return of results with genetic counseling. We evaluated participants’ responses to and the clinical utility of the reporting of actionable genetic findings. Twenty-two of 40 contacted carriers of 17 pathogenic BRCA1/2 variants responded and chose to receive results. Eight of these 22 participants qualified for high-risk assessment based on National Comprehensive Cancer Network criteria. Twenty of 21 counseled participants appreciated being contacted. Relatives of 10 participants underwent cascade screening. Five of 16 eligible female BRCA1/2 variant carriers chose to undergo risk-reducing surgery, and 10 adhered to surveillance recommendations over the 30-month follow-up period. We recommend the return of results to population-based biobank participants; this approach could be viewed as a model for population-wide genetic testing. The genotype-first approach permits the identification of individuals at high risk who would not be identified by application of an approach based on personal and family histories only.



中文翻译:

检测遗传性乳腺癌和卵巢癌风险的基因型优先方法以及向生物库参与者披露风险的影响

基因型优先的方法可以系统地识别BRCA1 / 2基因致病变异的携带者,这些变异赋予家族性乳腺癌和卵巢癌的高风险。爱沙尼亚生物样本库的参与者表示支持披露具有临床意义的发现。对于爱沙尼亚生物库队列,我们​​采用基因型优先的方法,联系携带者,并通过遗传咨询提供结果返回。我们评估了参与者对可操作的遗传发现报告的反应和临床效用。40 名接触过的 17 种致病性BRCA1 / 2变异携带者中,有 22 名做出了回应并选择接收结果。根据国家综合癌症网络标准,这 22 名参与者中有 8 名符合高风险评估资格。21 名接受咨询的参与者中,有 20 名感谢与我们联系。10 名参与者的亲属接受了级联筛查。16 名符合条件的女性BRCA1 / 2变异携带者中,有 5 名选择接受降低风险的手术,其中 10 名在 30 个月的随访期内遵守了监测建议。我们建议将结果返回给基于人群的生物样本库参与者;这种方法可以被视为全人群基因检测的模型。基因型优先的方法可以识别高风险个体,而仅根据个人和家族史的方法无法识别这些个体。

更新日期:2020-11-23
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