Paediatric brain tumours in South Africa – Prof Anthony Figaji
Prof Anthony Figaji
Title of the project
Paediatric brain tumours in South Africa.
Brain tumours are the second commonest cancer in children, but little is known about them. Even though in children they account for about as much as all the other solid tumours in the body combined, the general public and clinicians tend to know much less about brain cancer in children than leukaemia.
Despite some progress being made over the last 2 decades, overall patient outcomes remain poor when compared with other childhood cancers. Even in the so-called developed world, brain tumours accounts for most of the cancer-related deaths in children.
There remains much uncertainty about the nature of various brain tumours and their prognosis. In particular, virtually nothing is known about children with brain tumours in a South African setting and no current research projects address this. Fortunately, there is a growing awareness of the lack of research in non-communicable diseases in South Africa, which is timely because there has been exciting progress in tumour biology research elsewhere, especially in the last 5 years, that promises to open new avenues to better classify and treat various brain tumours. These are revealing important genetic origins of these cancers and may lead to targeted treatment for individual subgroups of brain tumours. These subclassifications likely will be a requirement in the future for international clinical trials.
In South Africa we have not yet engaged in any brain cancer biology research and so we need to urgently build a foundation, not only to be able to conduct our own molecular biology research, but also to be able to participate in international trials. Through this project, we expect to generate substantial epidemiological and clinical information which will be novel for South Africa.
We will examine geographic differences in brain tumours between children from Africa compared with North American and European data. We expect this project to establish a foundation for paediatric brain tumour research in South Africa and generate further interest in the field.
Importantly, we will establish a foundation for molecular biology in brain cancer research and we will develop a biobank of cancer specimens which has become almost routine at leading centres in the world but not in South Africa. The novel development of capacity for tumour molecular biology will establish important bench-to-bedside research in a neglected area of cancer in South Africa.
Breast cancer consists of four major subtypes that differ in their response to treatment. Genetic testing aimed at cancer prevention or treatment targeted at the cause of the disease can be performed by using a focused approach of testing well-characterised mutations based on a clinical suspicion of which genes may be involved, or panel testing that includes multiple mutations in many genes simultaneously. Currently available panels do not include all the genes associated with familial and sporadic cancer as the clinical relevance of actionable single nucleotide polymorphisms (SNPs) associated with a low, but increased risk, is controversial.
The importance of a family history of cancer is well-known to determine the appropriateness of genetic testing of high-penetrance genes such as BRCA1 and BRCA2 to confirm or exclude inheritance of mutations in these genes as the cause of early-onset cancer. The purpose of the study is to develop standardized referral guidelines and ultimately reimbursement policies for low-moderate penetrance genetic susceptibility testing.
South African patients diagnosed with primary breast carcinoma, some of whom were previously subjected to BRCA mutation analysis with written consent for research participation, will be subjected to testing for polymorphic variants in low-penetrance genes involved in the dysfunctional regulation of oestrogen metabolism and clearance as well as intermediate-risk variants involved in the DNA mismatch repair pathway. An open-innovation combined research and service platform is positioned as the ideal means of accomplishing this aim, by enabling the consideration of genetic information as part of a multidisciplinary clinical framework which integrates comprehensive patient data gleamed from diverse fields of healthcare and linked via the common thread of pathology.
Similar to the multifunctional pathogenic role of high-penetrance BRCA mutations, polymorphic variants in low-penetrance XME and SOD2 genes, as well as intermediate risk variants involved in the DNA mismatch repair pathway, are important risk determinants for other lifestyle-related cancers as well. While our initial focus on breast cancer is based on our research experience in the field, this recognition provides the basis for extension of the proposed project outcomes to other locally relevant neoplasms in future.
Radiotherapy, Paediatric oncology and Paediatric Pathology, collaborating with Prof Jeanette Parkes, Prof Alan Davidson, and Prof Komala Pillay.