Seymour Heather Jessica, Wainstein Tasha, Macaulay Shelley, Haw Tabitha, Krause Amanda
Division of Human Genetics, National Health Laboratory Service, Johannesburg, South Africa.
S Afr Med J. 2016 Feb 3;106(3):264-7. doi: 10.7196/SAMJ.2016.v106i3.10285.
Germline pathogenic mutations in cancer susceptibility genes result in inherited cancer syndromes. In the Afrikaner population of South Africa (SA), three founder mutations in the BRCA genes that lead to hereditary breast and ovarian cancer syndrome (HBOCS) have been identified.
To investigate the uptake and type of molecular testing performed on patients for HBOCS, to determine the prevalence of the three Afrikaner founder BRCA mutations as well as non-founder BRCA mutations in the study population, and to analyse the utility of two mutation prediction models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and Manchester scoring method) in assisting with the decision for the most cost-effective testing option.
A retrospective file review was performed on counsellees of self-reported Afrikaner ancestry from Johannesburg, SA (2001 - 2014), with a personal or family history of breast and/or ovarian cancer. Demographic and family history information was recorded and Manchester and BOADICEA scores were calculated for each patient.
Of 86 unrelated counsellees whose files were reviewed, 54 (62.8%) underwent BRCA genetic testing; 18 (33.3%) tested positive for a mutation, and 14 of these (77.8%) for an Afrikaner founder mutation. Twelve counsellees had the BRCA2 c.7934delG mutation. Four non-founder mutations were identified. BOADICEA scores were significantly higher in counsellees who tested positive for a mutation than in those who tested negative.
Founder mutation testing should be performed as a first-line option. BOADICEA is very useful in identifying counsellees at high risk for a BRCA mutation and also assists with the decision to pursue further testing following a negative founder mutation result. These findings assist in guiding an informed genetic counselling service for at-risk individuals with an Afrikaner background.
癌症易感基因中的种系致病突变会导致遗传性癌症综合征。在南非的阿非利卡人群体中，已鉴定出BRCA基因中的三种奠基者突变，这些突变会导致遗传性乳腺癌和卵巢癌综合征（HBOCS）。
调查对HBOCS患者进行的分子检测的接受情况和类型，确定研究人群中三种阿非利卡人奠基者BRCA突变以及非奠基者BRCA突变的患病率，并分析两种突变预测模型（疾病发病率和携带者估计算法的乳腺癌和卵巢癌分析（BOADICEA）和曼彻斯特评分法）在协助做出最具成本效益的检测选择决策方面的效用。
对来自南非约翰内斯堡（2001 - 2014年）、有乳腺癌和/或卵巢癌个人或家族病史且自我报告为阿非利卡人血统的咨询者进行回顾性档案审查。记录人口统计学和家族史信息，并为每位患者计算曼彻斯特和BOADICEA评分。
在审查其档案的86名无亲属关系的咨询者中，54名（62.8%）接受了BRCA基因检测；18名（33.3%）检测出突变呈阳性，其中14名（77.8%）为阿非利卡人奠基者突变。12名咨询者携带BRCA2基因c.7934delG突变。鉴定出四种非奠基者突变。检测出突变呈阳性的咨询者的BOADICEA评分显著高于检测呈阴性的咨询者。
应将奠基者突变检测作为一线选择。BOADICEA在识别BRCA突变高风险咨询者方面非常有用，并且在奠基者突变检测结果为阴性后协助做出进一步检测的决策。这些发现有助于为有阿非利卡人背景的高危个体提供明智的遗传咨询服务。
