Breast/Ovarian Cancer Susceptibility in SA Women: Clinical Utility of Multi-gene Panel Testing
Prof Lizette Jansen van Rensburg
Title of the project
Breast/ovarian cancer susceptibility in South African women: Clinical utility of multi-gene panel testing.
Breast cancer is a very common cancer worldwide. Cancer development is a multistage process, which results from a process of genetic changes, some inherited, some induced by environmental exposures and some occurring by chance. Much progress has been made in recent years in the identification of genetic lesions that predispose individuals to cancer. It has been estimated that ~ 20% of female breast cancers are due to inheritance of a number of genetic mistakes (mutations). Genetic testing for cancer predisposition genes is an important advance in cancer medicine. With the advent of next-generation sequencing, simultaneous sequencing of multiple cancer susceptibility genes is available through multiplex panels at a cost comparable to that for single gene testing. As we have been investigating breast (and ovarian) cancer susceptibility in South Africans (with the support of CANSA grants) for some time now and have gathered a substantial volume of data/information, we are of the opinion that it is now an opportune time to embark on a translational study. Previously we have found that individuals, carrying mistakes (mutations) in cancer risk genes, would be overlooked if testing for mutations is based solely on a family cancer history. It is important to identify these patients because the presence of such mistakes could affect treatment, follow-up and further cancer prevention in patients with breast or ovarian cancer and their relatives.
We propose to assess the clinical value of panel-based mutation screening (using targeted next-generation sequencing of cancer predisposition genes) of women with breast or ovarian cancer (unselected for family history of breast or ovarian cancer). This is in order to investigate the feasibility of translating this type of testing to clinical practice that will provide breast cancer units (surgeons, oncologists, etc) with enhanced ability to make informed decisions about patient care.
Our goal is to assess the clinical value of panel-based mutation screening (using targeted next generation sequencing of cancer predisposition genes) of women with breast or ovarian cancer (unselected for family history of breast or ovarian cancer). This is in order to investigate the feasibility of translating this type of testing to clinical practice that will provide breast cancer units (surgeons, oncologists, etc) with enhanced ability to make informed decisions about patient care.
Further results obtained with our stepwise approach of first investigating the BRCA-genes in the second set of DNA samples from women of European ancestry with breast cancer unselected for family history of cancer, shows that two founder mutations unique to South Africa, account for 75% of the women with a BRCA1/2 mutation.
The implications for the women who carry these deleterious mutations are on two levels, firstly it may influence the choice of chemotherapeutic drugs for their treatment and secondly, their risk of developing a second cancer has increased. Also, their first-degree relatives may be offered testing (after appropriate counselling) to determine who are unaffected carriers of these mutations, as they can benefit from increased surveillance and cancer preventative strategies.
- The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer (2019)
- BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry (2019)