Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants

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

doi:10.1038/s41431-020-00760-2

Cited by 26 publications

(23 citation statements)

References 40 publications

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“…In addition, more carriers thought they had a higher than average chance of developing melanoma at predisclosure and 6 months post-disclosure than non-carriers, which remained significant after excluding those with history of melanoma [ 204 ]. An Estonian study that returned pathogenic variants in BRCA1/2 genes to 22 biobanks participants found they generally felt calm and relaxed following genetic counselling, although a small number of participants reported feeling tense or worried [ 197 ]. A second Estonian study, in which 16p11.2 CNVs were reported back to 5 carriers, showed most were relieved and were coping with the information, although two said they were slightly worried [ 186 ].…”

Section: Experiences With Receiving or Returning Resultsmentioning

confidence: 99%

Return of individual research results from genomic research: A systematic review of stakeholder perspectives

et al. 2021

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Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders’ perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants.

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Section: Experiences With Receiving or Returning Resultsmentioning

confidence: 99%

Return of individual research results from genomic research: A systematic review of stakeholder perspectives

et al. 2021

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“…Research studies and biobanks that have elected to return genomic information to research participants typically share common themes and workflows. 22 , 23 , 24 , 25 First, participants must explicitly accept or decline gRoR at enrollment, or if this choice was not presented at enrollment, they must later be re-consented for gRoR. Next, a list of genes associated with actionable hereditary conditions is selected for analysis and potential return.…”

Section: Introductionmentioning

confidence: 99%

Returning actionable genomic results in a research biobank: Analytic validity, clinical implementation, and resource utilization

Zawatsky

Shah

Machini

et al. 2021

The American Journal of Human Genetics

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Summary Over 100 million research participants around the world have had research array-based genotyping (GT) or genome sequencing (GS), but only a small fraction of these have been offered return of actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to participant recontact revealed that GT falsely identified PLPVs in 44.9% of samples, and GT failed to identify 72.0% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1% and 2.5% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5% actively or passively declined further disclosure. 76.3% of those carrying PLPVs were unaware that they were carrying the variant, and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately $129,000 USD per year in laboratory testing and research staff support, representing $14 per participant whose DNA was analyzed or $3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.

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“…The GeneRISK-study ( Widén et al, 2020 ) invited 7,342 individuals to receive their PRS-enhanced risk score of cardiovascular disease via a web-based portal. In Estonia, the Estonian biobank has returned genetic results on breast and ovarian cancer ( Leitsalu et al, 2021 ) and familial hypercholesterolemia ( Alver et al, 2019 ). These studies have reported no major issues or mishaps in combing genomic data with more traditional risk factor data, and the information has generally been well received by the study participants.…”

Section: National Actions Towards the Concept Of Data-driven Precisio...mentioning

confidence: 99%

Reaching for Precision Healthcare in Finland via Use of Genomic Data

et al. 2022

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Concerns over future healthcare capacity along with continuing demands for sustainability call for novel solutions to improve citizens’ health and wellbeing through effective prevention and improved diagnosis and treatment. Part of the solution to tackle the challenge could be making the most of the exploitation of genomic data in personalized risk assessment, creating new opportunities for data-driven precision prevention and public health. Presently, the utilization of genomic data in the Finnish healthcare system is limited to a few medical specialty areas. To successfully extend the use of genomic information in everyday healthcare, evidence-based and feasible strategies are needed. The national actions that Finland is taking towards this goal are 1) providing scientific evidence for the utility of genomic information for healthcare purposes; 2) evaluating the potential health-economic impact of implementing precision healthcare in Finland; 3) developing a relevant legal framework and infrastructures for the utilization of genomic information; 4) building a national multidisciplinary expert network bringing together relevant professionals and initiatives to achieve consensus among the different stakeholders on specific issues vital for translating genomic data into precision healthcare; 5) building competence and genomic literacy skills among various target groups; and 6) public engagement (informing and educating the public). Taken together, these actions will enable building a roadmap towards the expedient application of genomic data in Finnish healthcare and promoting the health of our citizens.

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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

Abstract: doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Cited by 26 publications

References 40 publications

Return of individual research results from genomic research: A systematic review of stakeholder perspectives

Return of individual research results from genomic research: A systematic review of stakeholder perspectives

Returning actionable genomic results in a research biobank: Analytic validity, clinical implementation, and resource utilization

Reaching for Precision Healthcare in Finland via Use of Genomic Data

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