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Management of individuals with heterozygous germline pathogenic variants in RAD51C, RAD51D, and BRIP1: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Purpose - RAD51C, RAD51D, and BRIP1 germline pathogenic variants (GPVs) are associated with increased lifetime risks of tubo-ovarian cancer. Resources for managing RAD51C, RAD51D, and BRIP1 heterozygotes in clinical practice are limited. - Methods - An international workgroup developed a Clinical Pr...

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Main Authors: Ngeow, Joanne (Author) , Chiang, Jianbang (Author) , Astiazaran-Symonds, Esteban (Author) , Balmaña, Judith (Author) , Cass, Ilana (Author) , Kommoss, Felix (Author) , Foulkes, William D. (Author) , James, Paul A. (Author) , Katcher, Arielle (Author) , Klugman, Susan (Author) , Livinski, Alicia A. (Author) , Mak, Julie S. (Author) , Voian, Nicoleta (Author) , Wick, Myra J. (Author) , Tischkowitz, Marc (Author) , Pal, Tuya (Author) , Stewart, Douglas R. (Author) , Hanson, Helen (Author)
Format: Article (Journal)
Language:English
Published: 7 October 2025
In: Genetics in medicine
Year: 2025, Volume: 27, Issue: 11, Pages: 1-18
ISSN:1530-0366
DOI:10.1016/j.gim.2025.101557
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.gim.2025.101557
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1098360025002047
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Author Notes:Joanne Ngeow, Jianbang Chiang, Esteban Astiazaran-Symonds, Judith Balmaña, Ilana Cass, Felix K. F. Kommoss, William D. Foulkes, Paul A. James, Arielle Katcher, Susan Klugman, Alicia A. Livinski, Julie S. Mak, Nicoleta Voian, Myra J. Wick, Marc Tischkowitz, Tuya Pal, Douglas R. Stewart, Helen Hanson
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Summary:Purpose - RAD51C, RAD51D, and BRIP1 germline pathogenic variants (GPVs) are associated with increased lifetime risks of tubo-ovarian cancer. Resources for managing RAD51C, RAD51D, and BRIP1 heterozygotes in clinical practice are limited. - Methods - An international workgroup developed a Clinical Practice Resource to guide management of RAD51C, RAD51D, and BRIP1 heterozygotes using peer-reviewed publications and expert opinion. - Results - RAD51C, RAD51D, and BRIP1 are moderate (intermediate) penetrance ovarian cancer predisposition genes. Ovarian cancer risks for individuals with RAD51C, RAD51D, and BRIP1 GPVs may be influenced by family history and other modifiers. RAD51C and RAD51D GPVs are also associated with moderate risk of breast cancer, predominantly triple-negative subtype. RAD51C, RAD51D, and BRIP1 heterozygotes should be offered risk-reducing salpingo-oophorectomy close to the age of menopause based on age-specific risks and shared decision making. For RAD51C and RAD51D heterozygotes, enhanced breast surveillance may be indicated according to their personalized risk estimate and country-specific guidelines. Generally, risk-reducing mastectomy is not recommended. For RAD51C, RAD51D, and BRIP1 heterozygotes who develop cancer, there is insufficient evidence to guide any specific targeted treatment. - Conclusion - Systematic prospective data collection is needed to establish the outcomes of RAD51C, RAD51D, and BRIP1 associated cancers and particularly response to cancer treatment and survival.
Item Description:Gesehen am 11.03.2026
Physical Description:Online Resource
ISSN:1530-0366
DOI:10.1016/j.gim.2025.101557

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