Functional Analysis of Genetic Susceptibility Loci to Identify Biomarkers and Candidate Genes Associated with Ovarian Cancer Initiation, Progression and Outcome

Genetic factors can increase a woman's chance of getting ovarian cancer; they can also affect how well a woman responds to treatment when she has been diagnosed with ovarian cancer. Working as part of a large international team, the three principle investigators of this proposal have identified and characterized multiple genetic factors that can influence both a woman's risk of developing ovarian cancer and the chance of survival after a diagnosis of ovarian cancer. However, understanding how these genetic factors cause ovarian cancer and affect its treatment is largely unknown. Such an understanding requires a wide range of different expertise and an integrated research program; but the potential rewards and benefits of this research are substantial. As an example, two genes BRCA1 and BRCA2, identified in the mid-90s, significantly increase ovarian cancer risk; but understanding their function and clinical significance has led to intervention strategies to prevent ovarian cancer and novel therapeutic strategies to treat ovarian cancer. Undoubtedly their finding has saved countless lives. We aim to use resources, methodologies and technologies we have developed over the last few years to understand the function of novel genetic markers for ovarian cancer we have already found, and to discover additional markers that affect risk and survival in ovarian cancer patients. These studies will likely lead to the discovery of genes that are responsible for the early stage development of ovarian cancer, which could lead to the development of novel biomarkers for early detection and prevention of the disease; and also the discovery of genes that could lead to the development of novel therapies for treating ovarian cancers. Overall the goal of this research is significantly reduce mortality in women resulting from ovarian cancer.