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.

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。