Osler T S, Schoeman M, Pretorius W J S, Mathew C G, Edge J, Urban M F
Sydney Brenner Institute for Molecular Bioscience and Division of Human Genetics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Division of Human Genetics, Faculty of Health Sciences, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa.
Breast Cancer Res Treat. 2025 Apr;210(2):477-486. doi: 10.1007/s10549-024-07585-3. Epub 2025 Jan 7.
Breast cancer (BC) is the commonest cancer in South African women. A proportion are associated with a pathogenic or likely pathogenic (P/LP) variant in a BC susceptibility gene. Clinical guidelines for genetic testing are used to optimise variant detection while containing costs. We assessed the detection rate in women of diverse ancestries who met the South African National Department of Health (NDOH) testing guidelines, and analysed relationships between testing criteria, participant characteristics and presence of a BRCA1/2 P/LP variant.
Records from 376 women with BC who met NDOH criteria and had genetic testing were included. Demographic, clinical and test result data were collated to describe detection rates according to criteria met, and a multivariate analysis conducted to find variables most frequently associated with a P/LP variant.
P/LP variant prevalence in women meeting NDOH testing criteria was 19.9% (75/376). Women meeting ≥ 2 guideline criteria were over twice as likely to have a P/LP variant (OR 2.27, 95%CI 1.27-4.07, p = 0.006), highlighting the guidelines' capacity to stratify risk. Family history (OR 1.97; 95%CI 1.05-3.70, p = 0.03) and Black African ancestry (OR 2.58; 95%CI 1.28-5.18, p < 0.01) were independently associated with having a BRCA1/2 P/LP variant when controlling for other variables. Notably, although Black African participants were less likely to report a family history, those that did had higher odds of a P/LP variant in BRCA1/2.
These results demonstrate the usefulness of the NDOH guidelines in women of diverse ancestries and provide insight into the factors associated with P/LP variants in understudied African populations.
乳腺癌（BC）是南非女性中最常见的癌症。一部分病例与乳腺癌易感基因中的致病性或可能致病性（P/LP）变异有关。基因检测的临床指南用于优化变异检测，同时控制成本。我们评估了符合南非国家卫生部（NDOH）检测指南的不同血统女性的检测率，并分析了检测标准、参与者特征与BRCA1/2 P/LP变异存在之间的关系。
纳入376名符合NDOH标准并进行了基因检测的乳腺癌女性的记录。整理人口统计学、临床和检测结果数据，以根据符合的标准描述检测率，并进行多变量分析以找出与P/LP变异最常相关的变量。
符合NDOH检测标准的女性中P/LP变异患病率为19.9%（75/376）。符合≥2项指南标准的女性携带P/LP变异的可能性是前者的两倍多（OR 2.27，95%CI 1.27 - 4.07，p = 0.006），突出了指南对风险分层的能力。在控制其他变量时，家族史（OR 1.97；95%CI 1.05 - 3.70，p = 0.03）和非洲黑人血统（OR 2.58；95%CI 1.28 - 5.18，p < 0.01）与携带BRCA1/2 P/LP变异独立相关。值得注意的是，尽管非洲黑人参与者报告家族史的可能性较小，但报告家族史的参与者携带BRCA1/2中P/LP变异的几率更高。
这些结果证明了NDOH指南在不同血统女性中的有用性，并为未充分研究的非洲人群中与P/LP变异相关的因素提供了见解。
