Breast/ovarian cancer susceptibility in SA women Role of DNA homologous recombination genes – Prof Elizabeth Jv Rensburg
Prof Elizabeth Jansen van Rensburg
Breast/ovarian cancer susceptibility in South African women: Role of DNA homologous recombination genes.
Cancer of the breast is the most common cancer in South African women. One of the most important risk factors for breast cancer is a family history of the cancer, indicating that genetic factors are important determinants of breast cancer risk. Much progress has been made in the identification of genetic lesions that predispose individuals to breast cancer. It has been estimated that 15 – 20% of female breast cancers are due to inheritance of a mutation (mistake) in either of two genes called BRCA1 and BRCA2. Women who have inherited such mistakes are at a high risk of developing breast and/or ovarian cancer. By investigating a group of women with breast cancer (who have a strong family history of the cancer) as well as women not selected for age at diagnosis or family history of cancer, this study aims to clarify the role/impact of breast cancer susceptibility genes on the burden of breast cancer in South Africa.
Previously we have shown that 67% of high-risk South African breast cancer families (multiple affected women) carry an inherited BRCA1 or BRCA2 mutation. We have also found that 7% of an oncology clinic based group of Black women diagnosed with breast cancer before the age of 56 years (without a family history of cancer), carried a BRCA1 / BRCA2 mutation. These genes are important in maintaining the genetic stability of cells and have been shown to be linked to a specific DNA repair pathway known as, DNA homologous recombination repair (HR). Recent literature reported two new breast cancer susceptibility genes, RAD51D and XRCC2, that are also involved in HR-repair. It would now be useful to determine whether these genes are involved in the occurrence of breast cancer in South Africa. Identification of variants within these genes could lead to the development of additional screening techniques to identify high-risk individuals who can be offered counselling and help with the management of their risks.
In addition it is important to identify women whose breast cancer is associated with HR-DNA-repair dysfunction, since they could benefit from treatment with novel agents that target tumours which harbour defects in this pathway.
This study consisted of a number of phases in which different groups of women with breast cancer were screened for mistakes in the RAD51D and XRCC2 genes, by sequencing all the DNA regions that encode these genes. High-risk families (with multiple affected persons) were screened, as well as a group of women with breast cancer who do not have a strong family history of cancer.
Although various alterations were found in the genes, none are thought to be involved in increasing the risk for breast or ovarian cancer in South African women. Thus genetic testing for breast cancer susceptibility in South African women should not include the XRCC2 or RAD51D genes.
- Id of 4 novel susceptibility loci for oestrogen receptor negative breast cancer
- Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170
- No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women. Timothy R. Rebbeck, Elizabeth J. van Rensburg, et al. Breast Cancer Research (2016) 18:112.
- PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. Melissa C Southey, Elizabeth J van Rensburg, et al. JMG Online First, September 5, 2016 10.1136/jmedgenet-2016-103839
- Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3. Yosr Hamdi, Elizabeth J. van Rensburg, et al. Breast Cancer Res Treat (2017) 161:117–134.