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Purpose: This study explored healthcare professionals’ attitudes toward counselling patients on disclosing genetic cancer risk to relatives. Genetic counselling practices in Sweden are undergoing significant changes due to the increased use of genetic testing to assess hereditary risk and the implementation of mainstreamed testing in oncology care. These developments require an assessment of healthcare professionals’ perceived roles and responsibilities when working with patients with hereditary risk. Best practices need to be developed to effectively support risk disclosure, and subsequently risk management, to relatives.

Method: Data was collected through interviews with oncologists, gynaecologists, surgeons, clinical geneticists, and genetic counsellors, working in oncology care or at cancer genetics units. Data was analysed using reflective thematic analysis.

Results: The results are presented as four positions that healthcare professionals take, describing their attitudes towards counselling patients about risk disclosure to relatives. The position depends on whether they perceive healthcare or the patient as ultimately responsible for risk information reaching relatives, and whether their focus is on the patient or the at-risk relatives. There are several stakeholders involved, and hence 'characters in play'.

Conclusion: These results could serve as a basis for discussions on roles and responsibilities, while developing best practices regarding genetic counselling on hereditary cancer risk communication.

Purpose: As genetic testing becomes increasingly integrated into routine care, understanding its impact on psychological well-being and health-related quality of life (HRQoL) is essential. This study assessed HRQoL, anxiety and cancer worry following hereditary cancer testing in a Swedish clinical setting and identified predictors of these outcomes.

Methods: Participants were recruited from four outpatient cancer genetics clinics across Sweden. Eligible individuals either carried a pathogenic variant or met clinical criteria for familial breast or colorectal cancer. Questionnaires were completed shortly after receiving test results and again 6 months later. HRQoL was measured using the RAND-36, anxiety using the State-Trait Anxiety Inventory and cancer worry using the Cancer Worry Scale. Outcomes were compared with age- and sex-adjusted Swedish population data. Predictors of outcomes were analysed using multivariable linear regression.

Results: A total of 254 participants completed at least one questionnaire. HRQoL improved across all domains over 6 months, while anxiety and cancer worry declined. Participants without a recent cancer diagnosis had scores close to population norms at both time points. Those diagnosed within the previous year had lower HRQoL and higher anxiety and cancer worry, although they improved over time. Poorer outcomes were linked to a recent cancer diagnosis, being an index case, female sex and younger age, while education level and the test result itself were not associated with worse results.

Conclusion: Genetic testing was not associated with substantial short- or medium-term negative effects on HRQoL, anxiety or cancer worry. Individual risk factors should be considered when offering psychosocial support.

Plain English summary: Genetic testing is becoming more widely used, but earlier research on how testing affects everyday life often involved small groups or older data. Testing is also used in new ways today, which creates a need for updated studies to understand people's experiences and to see who might need extra support. In this study, we examined quality of life, anxiety and cancer-related worry in people tested for hereditary breast, ovarian or colorectal cancer. They completed questionnaires shortly after receiving their results and again 6 months later. We compared their answers with those from the general Swedish population. Quality of life improved over time, and anxiety and cancer worry decreased. People without a recent cancer diagnosis had scores similar to population norms. Those with a recent diagnosis had lower scores but also improved. Younger people, women and those recently diagnosed with cancer reported more anxiety and worry and lower quality of life scores. Education level and the test result itself did not affect these outcomes. Overall, genetic testing did not appear to cause lasting negative effects. Support may be most helpful for people with these risk factors.

We aimed to describe the clinical characteristics of families with heritable TP53-related cancer (hTP53rc) syndrome in Sweden with class 4 and 5 germline TP53 variants (gTP53), and to evaluate the genotype-phenotype correlation. These results were also used to evaluate our previously published phenotype prediction model based on TP53 missense variants and their impact on protein conformation. 90 families with hTP53rc were initially identified in Sweden. After variant reclassification using the TP53-specific ACMG criteria, 83 families remained (176 carriers) to harbour a pathogenic (class 5) or likely pathogenic (class 4) variant in TP53. Of these, 112 carriers (64%) had a previous history of cancer, and 35 (31%) had developed more than one primary tumour. 16% of the families met the stricter criteria for Classic Li-Fraumeni syndrome, 45% the updated Chompret criteria, 35% for hereditary breast cancer (HBC), and the remaining 5% were classified as “Others”. We identified 42 different gTP53 variants of which 22 were missense. The most frequently observed variant was the missense c.542 G > A, p.R181H identified in 14/29 (48%) of HBC families. Fifteen of the 20 informative missense variants (75%) were phenotypically predicted correctly using our previously published in silico prediction model. The TP53 p.R181H was identified as a common Swedish variant predominantly associated with an HBC phenotype. Apart from this variant, there were no significant genotype-phenotype correlations. Therefore, due to phenotypic overlap it is still too early to stratify surveillance programme for different TP53-carriers.

Key features: 

• The Northern Sweden Health and Disease Study (NSHDS) was initiated in the mid-1980s. The NSHDS is a population-based prospective longitudinal cohort comprising >140 000 participants in the two northernmost regions in Sweden, Norrbotten and Västerbotten, with >240 000 blood samples and 1.5 million person-years of follow-up.
• The NSHDS includes three sub-cohorts: the Västerbotten Intervention Programme (VIP), the expanded Northern Sweden Monitoring of Trends and Determinants of Cardiovascular Disease (MONICA) Study, and the Mammography Screening Project (MSP). The VIP is both a community-based cardiometabolic intervention programme encouraging healthy lifestyle (targeting individuals 40, 50, and 60 years of age), and a corresponding research cohort. The MONICA is an observational study focusing on cardiovascular disease and its associated risk factors, recruiting individuals aged 25–74 years. The MSP recruited women attending mammography during 1995–2006. The NSHDS median participation age is 50 years (53% women).
• Most participants contribute data on health, lifestyle, anthropometric measures, blood pressure, blood lipids, and glucose tolerance, along with research blood samples that are fractionated, frozen within an hour of collection, and stored at –80°C. Linkage to registries, clinical cohorts, and biological tissue archives facilitates studies of well-characterized participants (often combined with intervention studies).
• Collaborations are encouraged. Additional information can be found at: info.brs@umu.se; https://www.umu.se/en/biobank

Observational studies suggest that direct contact from healthcare to at-risk relatives may increase genetic counselling (GC) uptake as compared to family-mediated risk disclosure, but randomised controlled trials (RCTs) are lacking. This study assessed whether the offer of direct letters to relatives at risk of hereditary breast and ovarian cancer (HBOC) or Lynch syndrome increases GC uptake compared to family-mediated communication alone. Between 2020 and 2023, probands were randomly assigned to family-mediated disclosure (control) or family-mediated disclosure plus the offer of sending direct letters to at-risk relatives (intervention). The primary outcome was GC uptake within 12 months, measured as the proportion of eligible relatives at risk contacting a Swedish cancer genetics clinic. In total, 165 families (median: 4 eligible relatives, range: 1–26) were randomised to control (n = 79) or intervention (n = 86). GC uptake was 67% in controls and 71% in the intervention group (P = 0.23). After adjusting for predefined variables and covariates, there was still no significant difference between groups (OR: 1.24, CI: 0.79–1.95, P = 0.34). Distant relatives had lower uptake than first-degree relatives (OR: 0.27, CI: 0.18–0.40, P < 0.001), while female relatives had higher uptake than males (OR: 2.17, CI: 1.50–3.12, P < 0.001). This is the largest RCT so far investigating direct letters to relatives. GC uptake was high in both groups, and the intervention of direct letters did not show superiority over family-mediated communication alone. Direct letters to relatives may complement family-mediated disclosure in certain situations, but should not be implemented as a general procedure in cancer genetics practices. (Figure presented.)

An international workshop was held in Leuven, Belgium, on June 19–20, 2023, to discuss the communication of genetic risk information within families in the context of personalized prevention. Organized as part of the Horizon Europe project PROPHET (PeRsOnalised Prevention roadmap for the future HEalThcare in Europe), the event gathered interdisciplinary stakeholders to explore the benefits and challenges of various policy approaches for returning genetic test results with implications for family members. Five key themes emerged from the discussions: (1) recognizing family communication as an ongoing process, (2) adopting a family-centered approach rather than an individual one, (3) clarifying roles and responsibilities in the communication process, (4) addressing the lack of clear guidelines and policies, and (5) ensuring sufficient resources. To enhance family communication of genetic risk information, participants emphasized the importance of improving pre-test counseling and follow-up procedures, implementing policies to clarify roles and responsibilities, and providing training for healthcare professionals both within and outside genetic services.

Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.

Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.

Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).

Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.

Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.

Objectives: Hereditary cancer risks can be effectively managed if at-risk relatives enroll in surveillance and preventive care. Family-mediated risk disclosure has internationally been shown to be incomplete, selective and leave over a third of eligible at-risk individuals without access to genetic counseling. We explored patients handling of cancer risk information in practice. 

Methods: We conducted twelve semi-structured interviews with patients who had completed their genetic counseling and been asked to disclose risk information to relatives. Questions were designed to investigate lived experiences of communicating hereditary risk and focused on disclosure strategies, intrafamilial interactions and emotional responses. 

Results: Qualitative content analysis yielded five categories. These span personal fears, shared responsibilities, feeling of empowerment, innovative solutions and unmet needs. Patients put high value on collaboration with their genetic healthcare professionals but also solicited better overview of the counseling process and more personalized, case-tailored information. 

Conclusions: Our results add novel insights about the practical strategies employed by genetic counselees and their motivations behind disclosing hereditary risk information to relatives. 

Practice implications: A patient-centered cancer genetics care would clarify roles and responsibilities around risk disclosure, inform counselees about the process upfront and tailor information to offer case-specific data with the family’s inheritance pattern explained.

In a multicentre randomised controlled trial (DIRECT), we evaluate whether an intervention of providing direct letters from healthcare professionals to at-risk relatives (ARRs) affects the proportion of ARRs contacting a cancer genetics clinic, compared with patient-mediated disclosure alone (control). With the aim to explore how the patients included in the trial perceived and performed risk communication with their ARRs we analysed 17 semi-structured interviews with reflexive thematic analysis. All patients described that they disclosed risk information to all close relatives themselves. No integrity-related issues were reported by patients offered the intervention, and all of them accepted direct letters to all their ARRs. Patients’ approaches to informing distant relatives were unpredictable and varied from contacting all distant ARRs, sharing the burden with the family, utilising the offer of sending direct letters, vaguely relying on others to inform, or postponing disclosure. Most patients limited their responsibility to the disclosure, although others wanted relatives to get genetic counselling or felt a need to provide additional information to the ARRs before ending their mission. We also identified confusion about the implication of test results, who needed risk information, and who was responsible for informing ARRs. These misunderstandings possibly also affected risk disclosure. This study revealed that despite accepting the direct letters to be sent to all relatives, the patients also contributed to risk disclosure in other ways. It was only in some situations to distant relatives that the healthcare-assisted letter was the only means of communication to the ARRs.