Grant: Project Grant

Since the discovery of the BRCA1 and BRCA2 genes over 20 years ago, research has shown that carriers of mutations in these genes significantly increases their risk for ovarian cancer. Cancer prevention studies have since shown that the removal of ovaries (and fallopian tubes) from healthy women has proven effective in reducing or even eliminating risk in mutation carrier women. The knowledge gained by studying these genes has led to the development and implementation 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 generating sequencing technology to begin to identify new risk genes in ovarian cancer families that are not explained by the known or proposed new risk genes. This technology allows us to scan hundreds of genes in the human genome 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. This proposal describes our strategy for identifying and characterizing our most promising candidate genes. 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.