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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 volume 29, pages 471–481 (2021)Cite this article

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Abstract

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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Acknowledgements

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

Funding

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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Author notes

  1. These authors contributed equally: Liis Leitsalu, Marili Palover

Authors and Affiliations

  1. Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia

    Liis Leitsalu, Marili Palover, Timo Tõnis Sikka, Anu Reigo, Mart Kals, Kalle Pärn, Tiit Nikopensius, Tõnu Esko, Andres Metspalu & Neeme Tõnisson

  2. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

    Marili Palover, Timo Tõnis Sikka & Andres Metspalu

  3. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

    Mart Kals & Kalle Pärn

  4. Hematology and Oncology Clinic, Tartu University Hospital, Tartu, Estonia

    Peeter Padrik

  5. Institute of Clinical Medicine, University of Tartu, Tartu, Estonia

    Peeter Padrik

  6. Dept. of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia

    Neeme Tõnisson

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  1. Liis Leitsalu
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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). https://doi.org/10.1038/s41431-020-00760-2

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