Genome‐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.
Background:Identification of hereditary predisposition to cancer has limited significance if not followed by efficient cancer prevention in the family. Probands are traditionally left to inform their ...relatives about the increased risk, but distant relatives may remain uninformed. An approach to contacting directly at-risk persons assumed to be unaware of their increased cancer risk was taken. With cancer prevention as the ultimate goal, the study was aimed at investigating attitudes towards and psychosocial consequences of this novel strategy.Methods:In families with hereditary non-polyposis colorectal cancer (Lynch syndrome), 286 healthy adult relatives with a 50% risk of a predisposing mutation were contacted by letter. Of these, 112 participated in counselling and predictive testing. Baseline information and information obtained 1 month after the test for 73 respondents were compared with 299 corresponding subjects, approached via the proband (family-mediated approach in our previous study) in these families.Results:After the contact letter, 51% consented to the study. Of these, 92% approved of the direct contact and 33% had tried to seek information. In 34% of the mutation carriers, neoplasia was identified in the first post-test colonoscopy. Although post-test fear of cancer increased among the mutation carriers and decreased among noncarriers, almost all participants were satisfied with their decision to participate, independently of their test results, parallel to the family-mediated approach.Conclusion:In this large-scale study, relatives in cancer families were actively contacted to inform them of the condition and genetic counselling. Their attitudes were encouraging, and the psychosocial consequences were similar to the family-mediated approach. Our results suggest the appropriateness of direct contact as an alternative method of contact in cases of life-threatening treatable disease.
Genome-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.
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.
Background & Aims: Identification of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome enables prevention of colorectal cancer (CRC) by means of colonoscopy and polypectomies. We ...evaluated the efficacy of screening in a controlled trial over 15 years.
Methods: Incidence of CRC and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known.
Results: CRC developed in 8 screened subjects (6%) compared with 19 control subjects (16 %;
P = 0.014). The CRC rate was reduced by 62%. In mutation-positive subjects alone, the CRC rates were 18% in screened subjects and 41% in controls (
P = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All CRCs in the study group were local, causing no deaths, compared with 9 deaths caused by CRC in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (
P = 0.003), 4 vs. 12 in mutation-positive subjects (
P = 0.05).
Conclusions: Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.
GASTROENTEROLOGY 2000;118:829-834
Mutations in hepatic nuclear factor 1alpha cause a monogenic form of diabetes, maturity onset diabetes of the young type 3 (MODY3). Our aim was (1) to assess the uptake of genetic testing for MODY3 ...and to determine factors affecting it, and (2) to compare attitudes to predictive genetic testing between families with MODY3 and a previously studied group at risk of hereditary non-polyposis colorectal cancer (HNPCC).
Adult members of two extended MODY3 pedigrees, either with diabetes or a 50% risk of having inherited the mutation (n=144, age 18-60 years), were invited to an educational counselling session followed by a possibility to obtain the gene test result. Data were collected through questionnaires before counselling and 1 month after the test disclosure.
Eighty-nine out of 144 (62%) participated in counselling, and all but one wanted the test result disclosed. No significant sociodemographic differences were observed between the participants and non-participants. The counselling uptake was similar among diabetic and non-diabetic subjects. Uncertainty about the future and the risk for the children were the most common reasons to take the gene test. At follow-up, most subjects in both MODY3 (100%) and HNPCC (99%) families were satisfied with their decision to take the test and trusted the result. The majority of both diabetic and non-diabetic subjects considered that the MODY3 gene test should be offered either in childhood (50 and 37%) or as a teenager (30 and 37%).
Genetic testing for MODY3 was well accepted among both diabetic and non-diabetic participants. The subjects found the gene test reliable and they were satisfied with their decision regarding the predictive test.
OBJECTIVES To evaluate the feasibility of a reduced counselling programme for predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) in terms of counsellees' opinions on ...the extent and significance of genetic counselling and need for psychological support at different phases of the testing procedure. DESIGN Prospective follow up study with pre-test questionnaire assessment of background sociodemographic variables. The protocol comprised a pre-test counselling session, a period for reflection, and a test disclosure session. The outcome variables were studied by post-test questionnaires at one month and one year follow up. SUBJECTS Two hundred and seventy one high risk members of 36 families with HNPCC who attended both counselling sessions and completed the questionnaires. RESULTS The pre-test counselling was considered fairly or very useful by 89% of respondents and one post-test session was considered sufficient by over 80% of respondents at follow up. Fifty three percent would have used extra psychological support had it been offered with the counselling. On enquiry one year after receiving the test result, only 2% stated that the need for support was at its greatest at that time, while the majority (46%) reported that the need for support had been greatest at the moment of test disclosure. CONCLUSIONS A protocol that includes one comprehensive pre-test counselling session and a test disclosure session, supplemented with the option of professional psychological support, seems to be sufficient for both the educational and supportive needs of counsellees. Only a minority expressed a need for post-test follow up sessions, which suggests that, in this disorder, resources can be directed to the beneficial surveillance programmes rather than to extensive psychological support.
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