Lay summary
The recent development of new gene screening technologies has revolutionised genetic testing of high-risk breast and ovarian cancer patients. Genetic information from these technologies is vital for directing clinical care of patients and their families and has significant implications for disease prevention. Approximately 1/250 individuals inherit a genetic mutation in the genes BRCA1 or BRCA2, which means they are at high-risk of developing breast and ovarian cancer. However, the risk of cancer for these individuals varies significantly due to other (unknown) genetic changes, creating a significant challenge for counselling and clinical decision making. Our proposal aims to exploit a large international collaboration to identify and functionally characterise genetic changes which modify the risk of breast and ovarian cancer in women who have inherited a BRCA1/BRCA2 mutation. Discoveries from this unique proposal will facilitate accurate clinical decision making, and provide new insights into the aetiology of breast and ovarian tumour development.