“I would like to discuss it further with an expert” : a focus group study of Finnish adults’ perspectives on genetic secondary findings

Lowered costs of genomic sequencing facilitate analyzing large segments of genetic data. Ethical debate has focused on whether and what kind of incidental or secondary findings (SFs) to report, and how to obtain valid informed consent. However, people’s support needs after receiving SFs have received less attention. We explored Finnish adults’ perspectives on reporting genetic SFs. In this qualitative study which included four focus group discussions (N = 23) we used four vignette letters, each reporting a genetic SF predisposing to a different disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li-Fraumeni syndrome. Transcribed focus group discussions were analyzed using inductive thematic analysis. Major themes were immediate shock, dealing with worry and heightened risk, fear of being left alone to deal with SFs, disclosing to family, and identified support needs. Despite their willingness to receive SFs, participants were concerned about being left alone to deal with them. Empathetic expert support and timely access to preventive care were seen as essential to coping with shock and worry, and disclosing SFs to family. Discussion around SFs needs to concern not only which findings to report, but also how healthcare systems need to prepare for providing timely access to preventive care and support for individuals and families.Lowered costs of genomic sequencing facilitate analyzing large segments of genetic data. Ethical debate has focused on whether and what kind of incidental or secondary findings (SFs) to report, and how to obtain valid informed consent. However, people’s support needs after receiving SFs have received less attention. We explored Finnish adults’ perspectives on reporting genetic SFs. In this qualitative study which included four focus group discussions (N = 23) we used four vignette letters, each reporting a genetic SF predisposing to a different disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li-Fraumeni syndrome. Transcribed focus group discussions were analyzed using inductive thematic analysis. Major themes were immediate shock, dealing with worry and heightened risk, fear of being left alone to deal with SFs, disclosing to family, and identified support needs. Despite their willingness to receive SFs, participants were concerned about being left alone to deal with them. Empathetic expert support and timely access to preventive care were seen as essential to coping with shock and worry, and disclosing SFs to family. Discussion around SFs needs to concern not only which findings to report, but also how healthcare systems need to prepare for providing timely access to preventive care and support for individuals and families.Peer reviewe

Lay Perspectives on Receiving Different Types of Genomic Secondary Findings : a Qualitative Vignette Study

available at: https://rdcu.be/4BhDGenome-wide sequencing may generate secondary findings (SFs). It is recommended that validated, clinically actionable SFs are reported back to patients/research participants. To explore publics’ perspectives on the best ways to do this, we performed a vignette study among Finnish adults. Our aim was to explore how lay people react to different types of hypothetical genomic SFs. Participants received a hypothetical letter revealing a SF predisposing to a severe but actionable disease - cardiovascular disease (familial hypercholesterolemia, long QT syndrome) or cancer (Lynch syndrome, Li–Fraumeni syndrome). Participants (N=29) wrote down their initial reactions, and discussed (N=23) these in focus groups. Data were analyzed using inductive thematic analysis. Reactions to hypothetical SFs varied according to perceived severity and familiarity of the diseases. SFs for cancer were perceived as more threatening than for cardiovascular diseases, but less distressing than risk for psychiatric or neurological disorders, which participants spontaneously brought up. Illness severity in terms of lived experience, availability of treatment, stigma, and individual’s responsibility to control risk were perceived to vary across these disease types. In addition to clinical validity and utility, SF reporting practices need to take into account potential familiarity and lay illness representations of different diseases. Illness representations may influence willingness to receive SFs, and individuals’ reactions to this information.Peer reviewe

Genetic knowledge and attitudes towards health-related genetic information among Finns

BACKGROUND. In this study, we examined the genetic knowledge among Finns, their attitudes towards genetic testing, and which types of health-related genetic information they are interested in. METHODS. We invited a random sample of 4000 18 to 64-year-old citizens to participate. The online survey received 792 responses (response rate: 19.8%) in June-September 2017. The survey explored the level of genetic knowledge and the attitudes and experience concerning genetic testing. The survey included a video that provided four examples of health-related genetic information. RESULTS.The majority of participants considered that they had too little knowledge of genetic tests. Younger and more educated participants and those working in healthcare had a better knowledge of genetics than the others. Attitudes towards genetic testing were positive and the respondents felt that they should have autonomy in decisions related to genetic tests. The respondents wished to receive risk information on actionable hereditary diseases, multifactorial diseases, and carrier status. In contrast, they were more negative about risk information on non-actionable hereditary diseases. CONCLUSIONS. The majority of Finns perceive health-related genetic information as useful. They are interested in their personal genetic risk information.Peer reviewe

Uptake of genetic testing by the children of Lynch syndrome variant carriers across three generations

Many Lynch syndrome (LS) carriers remain unidentified, thus missing early cancer detection and prevention opportunities. Tested probands should inform their relatives about cancer risk and options for genetic counselling and predictive gene testing, but many fail to undergo testing. To assess predictive testing uptake and demographic factors influencing this decision in LS families, a cross-sectional registry-based cohort study utilizing the Finnish Lynch syndrome registry was undertaken. Tested LS variant probands (1184) had 2068 children divided among three generations: 660 parents and 1324 children (first), 445 and 667 (second), and 79 and 77 (third). Of children aged 418 years, 801 (67.4%), 146 (43.2%), and 5 (23.8%), respectively, were genetically tested. Together, 539 first-generation LS variant carriers had 2068 children and grandchildren (3.84 per carrier). Of the 1548 (2.87 per carrier) eligible children, 952 (61.5%) were tested (1.77 per carrier). In multivariate models, age (OR 1.08 per year; 95% CI 1.06-1.10), family gene (OR 2.83; 1.75-4.57 for MLH1 and 2.59; 1.47-4.56 for MSH2 compared with MSH6), one or more tested siblings (OR 6.60; 4.82-9.03), no siblings (OR 4.63; 2.64-8.10), and parent under endoscopic surveillance (OR 5.22; 2.41-11.31) were independent predictors of having genetic testing. Examples of parental adherence to regular surveillance and genetically tested siblings strongly influenced children at 50% risk of LS to undergo predictive gene testing. High numbers of untested, adult at-risk individuals exist even among well-established cohorts of known LS families with good adherence to endoscopic surveillance.Peer reviewe

Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

<p>Abstract</p> <p>Background</p> <p>von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the <it>VHL </it>gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children.</p> <p>Methods</p> <p>We tested 17 families (n = 109 individuals) for <it>VHL </it>mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the <it>VHL </it>gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations.</p> <p>Results</p> <p>Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02). Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01).</p> <p>Conclusions</p> <p>The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening procedures in non mutation-carriers. However, mutation-carriers showed poor adherence to long-term tumor surveillance. Therefore, many of them did not obtain the full benefit of early detection and treatment, which is central to the reduction of morbidity and mortality in VHL disease. Studies designed to improve adherence to vigilance protocols will be necessary to improve treatment and quality of life in patients with hereditary cancer syndromes.</p

Limitations and pitfalls of using family letters to communicate genetic risk: a qualitative study with patients and healthcare professionals

European genetic testing guidelines recommend that healthcare professionals (HCPs) discuss the familial implications of any test with a patient and offer written material to help them share the information with family members. Giving patients these “family letters” to alert any relatives of their risk has become part of standard practice and has gone relatively unquestioned over the years. Communication with at-risk relatives will become an increasingly pressing issue as mainstream and routine practice incorporates broad genome tests and as the number of findings potentially relevant to relatives increases. This study therefore explores problems around the use of family letters to communicate about genetic risk. We conducted 16 focus groups with 80 HCPs, and 35 interviews with patients, recruited from across the UK. Data were analyzed thematically and we constructed four themes: 1) HCPs writing family letters: how to write them and why?, 2) Patients’ issues with handing out family letters, 3) Dissemination becomes an uncontrolled form of communication, and 4) When the relative has the letter, is the patient’s and HCP’s duty discharged? We conclude by suggesting alternative and supplementary methods of communication, for example through digital tools, and propose that in comparison to communication by family letter, direct contact by HCPs might be a more appropriate and successful option