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. 2021 Mar;29(3):471-481. doi: 10.1038/s41431-020-00760-2. Epub 2020 Nov 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attitude
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Female
  • Genetic Carrier Screening / ethics
  • Genetic Carrier Screening / methods*
  • Genetic Counseling / psychology*
  • Genetic Counseling / standards
  • Hereditary Breast and Ovarian Cancer Syndrome / diagnosis
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics*
  • Hereditary Breast and Ovarian Cancer Syndrome / psychology
  • Hereditary Breast and Ovarian Cancer Syndrome / surgery
  • Humans
  • Patient Compliance*
  • Prophylactic Mastectomy / psychology
  • Prophylactic Mastectomy / statistics & numerical data
  • Truth Disclosure

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human