Grant: Operating Grant: Secondary Data Analysis for Cancer Prevention and Control

Since their discovery over 20 years ago, research has shown that carriers of mutations in BRCA1 or BRCA2 significantly increases their risk for breast and ovarian cancer. Cancer prevention studies have shown that the removal of ovaries and fallopian tubes from healthy women has proven effective in reducing or eliminating risk in mutation carrier women. The knowledge gained by studying these genes has led to the development of genetic tests and counseling services for the purposes of identifying mutation carrier women for offering cancer prevention options. However, hereditary ovarian cancer is not all explainable by BRCA1 and BRCA2 mutations. There is new evidence suggesting that rare mutations affecting proteins that are involved in the biology of repairing damage to the DNA of genes also play a role in conferring risk, as has been shown for BRCA1 and BRCA2. We have used next generation sequencing technology to find new risk genes in ovarian cancer families that are not explained by BRCA1 and BRCA2. This technology allows us to scan hundreds of genes for mutations in one experiment. We have used a strategy that focuses on the French Canadians of Quebec, a study population known for its contribution to medical genetics. We have identified promising candidates that play a role in DNA repair pathways. This proposal describes our strategy for investigating our most promising candidates using established biobanks. Understanding the role of new cancer risk genes to hereditary ovarian cancer will advance knowledge of its causation. Also, such genes have the strongest potential as genetic biomarkers that could be useful for developing ovarian cancer prevention and management strategies. In the long-term our research has the potential to impact policies for medical genetic testing for identifying women at increased risk for ovarian cancer for which the overall survival is less than 30% and where few treatment options are currently available.