Secondary findings in hereditary cancer genes after germline genetic testing : systematic review of literature

Avsec, Eva (author), Blatnik, Ana (author), Krajc, Mateja (author)

In the last decade the increasing use of germline genetic testing has led to frequent discoveries of secondary findings (SF) in hereditary cancer (HC) genes. Disclosure and clinical management of such findings are still not clearly defined and raise many ethical, clinical, and practical questions. This systematic review is focused on frequency of reported SF in HC genes across different populations as well as summarizing current guidelines, recommendations, and actual clinical practice about reporting and managing SF in HC genes. A systematic literature search according to the PRISMA guidelines was performed on the electronic database PubMed from inception to June 2024. 30 research papers involving almost 150,000 patients were reviewed. The reported frequencies of SF in HC genes varied between 0.4 and 3.1%. The majority of patients agreed to receive SF for medically actionable genes. Management and surveillance of patients after disclosure of SF in HC genes were rarely reported, but the limited data show no regret of receiving such results as well as diagnoses of early-stage cancer in patients participating in recommended surveillance programs related to SF. A substantial number of carriers of highly penetrant pathogenic variants in HC genes is discovered by reporting SF after germline genetic testing with next-generation sequencing. Additional information about the impact of SF disclosure on individuals and health care systems is needed to optimize the integration of SF into clinical care.

• Language: English
• Keywords: hereditary cancer, genetic testing, systematic review
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 595–604
• Numbering: Vol. 144, iss. 6
• PID: 20.500.12556/RUL-178482
• UDC: 616-07
• ISSN on article: 0340-6717
• DOI: 10.1007/s00439-025-02746-w
• COBISS.SI-ID: 235578627
• Publication date in RUL: 28.01.2026

Record is a part of a journal

• Title: Human genetics
• Shortened title: Hum. genet.
• Publisher: Springer Nature
• ISSN: 0340-6717
• COBISS.SI-ID: 1513999

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: dedni raki, genetski testi, sistematični pregled

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0289
• Name: Značilnosti malignih neoplazem, pomembne za diagnozo ter napoved poteka bolezni in izida zdravljenja