Beyond BRCA: Genetic testing for gynaecological cancers in South Africa

Hereditary cancer syndromes, caused by pathogenic variants in specific genes, substantially increase an individual's risk for cancer, and are estimated to cause 10% of all uterine cancers and 20% of all ovarian cancers. However, these data are primarily based on high-income countries, and to date there are no published data on the known pathogenic variants or testing of cancer predisposition genes associated with gynaecological cancers in South Africa.

To investigate the uptake and type of molecular testing performed on patients with a suspected hereditary cancer syndrome associated with gynaecological cancer, and to assess whether patient characteristics impacted the detection of pathogenic variants.

A retrospective file review was performed for patients with a confirmed diagnosis or family history of gynaecological cancer, seen by a single clinical genetics centre in Johannesburg between 2003 and 2023. Demographic information, family history and medical information were recorded and analysed.

A total of 104 records were included in analysis. The majority (73/104, 70.2%) of patients were seen in the private healthcare system, of whom most (41%) were of European ancestry. Of the remaining 31 public healthcare patients, the majority were of indigenous African ancestry (42%). Most (78/104, 75.0%) underwent diagnostic genetic testing. Of these, 25 (32.1%) were positive for pathogenic variants, 41 (52.6%) were negative and 12 (15.4%) returned a variant of unknown significance. Test results were significantly different between patients of European and non-European ancestry (p<0.05), with those of non-European ancestry 30% less likely to have a pathogenic variant detected (odds ratio 0.7, 95% confidence interval 0.22 - 2.21).

A disparity exists not only in genetic testing availability but also clinic attendance between the public and private healthcare systems, which likely limits the ability to diagnose hereditary cancer syndromes associated with gynaecological cancers in public healthcare hospitals.