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生殖系基因检测后遗传性癌症基因的次要发现——文献系统综述

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

作者信息

Avsec Eva, Blatnik Ana, Krajc Mateja

机构信息

Department of Clinical Cancer Genetics, Institute of Oncology Ljubljana, Zaloška 2, Ljubljana, 1000, Slovenia.

Faculty of Medicine, University of Ljubljana, Korytkova 2, Ljubljana, 1000, Slovenia.

出版信息

Hum Genet. 2025 Apr 28. doi: 10.1007/s00439-025-02746-w.


DOI:10.1007/s00439-025-02746-w
PMID:40293485
Abstract

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.

摘要

在过去十年中,生殖系基因检测的使用日益增加,导致在遗传性癌症(HC)基因中频繁发现次要发现(SF)。此类发现的披露和临床管理仍未明确界定,并引发了许多伦理、临床和实际问题。本系统综述聚焦于不同人群中HC基因报告的SF频率,同时总结关于HC基因中SF报告和管理的当前指南、建议及实际临床实践。根据PRISMA指南,对电子数据库PubMed从创建到2024年6月进行了系统的文献检索。对涉及近150,000名患者的30篇研究论文进行了综述。HC基因中报告的SF频率在0.4%至3.1%之间。大多数患者同意接受针对具有医学可操作性基因的SF。HC基因中SF披露后患者的管理和监测报告很少,但有限的数据显示,接受此类结果的患者没有后悔,并且参与与SF相关的推荐监测项目的患者被诊断出早期癌症。通过下一代测序进行生殖系基因检测后报告SF,发现了大量携带HC基因中高 penetrant 致病变异的携带者。需要更多关于SF披露对个人和医疗保健系统影响的信息,以优化SF在临床护理中的整合。

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

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本文引用的文献

[1]
Commentary: Why is genetic testing underutilized worldwide? The case for hereditary breast cancer.

BJC Rep. 2024-10-1

[2]
Secondary findings in genes related to cancer phenotypes in Turkish exome sequencing data from 2020 individuals.

Am J Med Genet A. 2024-11

[3]
Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.

Am J Obstet Gynecol. 2024-9

[4]
Additional findings from the 100,000 Genomes Project: A qualitative study of recipient perspectives.

Genet Med. 2024-6

[5]
Secondary (additional) findings from the 100,000 Genomes Project: Disease manifestation, health care outcomes, and costs of disclosure.

Genet Med. 2024-3

[6]
Actionable Genotypes and Their Association with Life Span in Iceland.

N Engl J Med. 2023-11-9

[7]
ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG).

Genet Med. 2023-8

[8]
Hereditary cancer syndromes.

World J Clin Oncol. 2023-2-24

[9]
Clinical and psychological implications of secondary and incidental findings in cancer susceptibility genes after exome sequencing in patients with rare disorders.

J Med Genet. 2023-7

[10]
Clinical exome-based panel testing for medically actionable secondary findings in a cohort of 383 Italian participants.

Front Genet. 2022-11-10

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