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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


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.

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Fig. 1: Framework for the return of results.
Fig. 2: Added value of the genotype-first approach to the identification of high-risk individuals.


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We express our sincere thanks to the biobank participants and their relatives for participating in the study.


This research was supported by the European Union through the European Regional Development Fund (project no. 2014-2020.4.01.15-0012 GENTRANSMED), European Union Horizon 2020 (grant no. 810645, no. 654248), Estonian Research Council (PUT736 to NT, PUT PRG555 to NT, IUT20-60, PUT1660 to TE, PUTJD817 to MK, MOBERA15, RITA1/01-42-03).

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Correspondence to Neeme Tõnisson.

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Leitsalu, L., Palover, M., Sikka, T.T. et al. Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants. Eur J Hum Genet 29, 471–481 (2021).

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