Ovarian cancer remains the deadliest gynecologic malignancy. Prior studies have indicated that around 20% of ovarian cancers are associated with identifiable inherited mutations (for example mutations in the genes BRCA1 and BRCA2). These mutations increase the risk of developing ovarian cancer, one of the highest proportions of any solid tumor. When these inherited risk mutations are identified in advance, patients have the opportunity to undergo highly effective and lifesaving interventions such as preventative removal of the fallopian tubes and ovaries.
Prior detailed examinations of ovarian cancer risk factors have been assessed in this population and other study populations, but no study has been done defining inherited mutations in this group.
The central problem this work addresses is the need to decrease ovarian cancer mortality through improving ovarian cancer prevention. Our goals are to 1) determine the frequency of inherited mutations in ovarian cancer cases and non-cases in the UK Biobank using whole exome sequencing (WES) data, 2) to examine how these inherited mutations relate to clinical characteristics of the ovarian cancer patients, and 4) to see how inherited mutations interact with other known risk factors for ovarian cancer within the unique population of the UK Biobank. It is rare to have detailed information about hormone use, parity, age, and ovarian cancer clinical characteristics in a group of patients with ovarian cancer who also have pre-diagnosis DNA samples. Our proposal is unique, in that other studies evaluating gene-environment interactions have focused on common variants and single nucleotide polymorphisms rather than our focus on pathogenic mutations. We anticipate our project will take 30 months from data access to publication.
The assessment of interactions between genomic risk factors and other potentially modifiable risk factors for ovarian cancer will help guide the health behaviors of patients at risk. We are committed to reducing deaths from ovarian cancer through better prevention.