Genetics in medicine : official journal of the American College of Medical Genetics · 2025
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).
СтатьяКлинические рекомендацииПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Ngeow Joanne, Chiang Jianbang, Astiazaran-Symonds Esteban, Balmaña Judith, Cass Ilana, Kommoss Felix K F, Foulkes William D, James Paul A, Katcher Arielle, Klugman Susan, Livinski Alicia A, Mak Julie S, Voian Nicoleta, Wick Myra J, Tischkowitz Marc, Pal Tuya, Stewart Douglas R, Hanson Helen, ACMG Professional Practice and Guidelines Committee. Electronic address: documents@acmg.net
Аннотация
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.
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.