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Direct letters to relatives at risk of hereditary cancer—a randomised trial on healthcare-assisted versus family-mediated risk disclosure
Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; Department of Clinical Genetics, Pathology and Molecular Diagnostics, Skåne University Hospital, Lund, Sweden.
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.ORCID iD: 0000-0003-2218-6881
Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
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2025 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438Article in journal (Refereed) Epub ahead of print
Abstract [en]

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.)

Place, publisher, year, edition, pages
Springer Nature, 2025.
National Category
Medical Genetics and Genomics
Identifiers
URN: urn:nbn:se:umu:diva-243089DOI: 10.1038/s41431-025-01922-wISI: 001541952600001PubMedID: 40745491Scopus ID: 2-s2.0-105012453486OAI: oai:DiVA.org:umu-243089DiVA, id: diva2:1992994
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00964Swedish Cancer Society, 2020-1107Swedish Research Council, 2022-02226Region Västerbotten, RV980080Region Västerbotten, RV-928271 tAvailable from: 2025-08-28 Created: 2025-08-28 Last updated: 2025-08-28

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Hawranek, CarolinaWennstedt, SigridNuman Hellquist, BarbroRosén, Anna

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