Research

Breast cancer in high-risk Afrikaner families: Is BRCA founder mutation testing sufficient?

Heather Jessica Seymour, Tasha Wainstein, Shelley Macaulay, Tabitha Haw, Amanda Krause

Abstract


Background. 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.

Objectives. 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.

Methods. 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.

Results. 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.

Conclusions. 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.


Authors' affiliations

Heather Jessica Seymour, Division of Human Genetics, National Health Laboratory Service, Johannesburg, South Africa

Tasha Wainstein, Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Shelley Macaulay, Division of Human Genetics, National Health Laboratory Service, Johannesburg, South Africa; Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Tabitha Haw, Division of Human Genetics, National Health Laboratory Service, Johannesburg, South Africa; Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Amanda Krause, Division of Human Genetics, National Health Laboratory Service, Johannesburg, South Africa; Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Full Text

PDF (134KB)

Keywords

Hereditary breast and ovarian cancer; Afrikaner founder mutations; Genetic; Cancer

Cite this article

South African Medical Journal 2016;106(3):264-267. DOI:10.7196/SAMJ.2016.v106i3.10285

Article History

Date submitted: 2015-11-04
Date published: 2016-02-03

Article Views

Abstract views: 2809
Full text views: 1134

Comments on this article

*Read our policy for posting comments here