Cancer Risks Associated with Inherited Mutations in Ovarian Cancer Susceptibility Genes Beyond BRCA1 and BRCA2
Abstract
Ovarian cancer is the most deadly cancer of the female reproductive tract. Women with early stage ovarian cancer have a high cure rate, but there is no good test that can detect ovarian cancer at an early, curable stage. A large fraction of ovarian cancer is hereditary; women get cancer because they have inherited an alteration or mutation in a cancer gene that they inherited from either their mother or father. Inherited mutations in two genes, BRCA1 and BRCA2, account for about 15% of all ovarian cancers. Women with BRCA1 and BRCA2 mutations have a very high lifetime risk of ovarian cancer (20%-40%). For these women, the current recommendation is to undergo preventive surgery to remove the ovaries and fallopian tubes after completing childbearing. This surgery induces early menopause, but saves lives by decreasing the risk of both breast and ovarian cancer. Our group has recently discovered that inherited mutations in another dozen genes cause another 5%-6% of cases. However, for these genes, the lifetime risk of ovarian cancer is less certain and the role of preventive surgery has not been established. One-third of women who get hereditary ovarian cancer have no known family history of breast or ovarian cancer, so relying on family history will not identify all women at risk. In the near future, women could get a single genetic test that would identify mutations in all ovarian cancer genes. The technology already exists to sequence many genes cheaply in a single cancer risk test, but before such a test could be broadly used to prevent ovarian cancer, we need a better understanding of risks associated with various ovarian cancer genes. Most previous studies of ovarian cancer genetics have focused only on the BRCA1 and BRCA2 genes and have studied mostly white women. Our study will correct the knowledge deficit by evaluating all known ovarian cancer genes and, for the first time, include a large number of African American women with ovarian cancer. We will also discover new ovarian cancer genes by testing all genes in families with multiple women with ovarian cancer. Our immediate goal is to refine the understanding of inherited ovarian cancer risks. The long-term goal is to use this information to devise tailored cancer prevention plans for women based on their identified risk in order to eliminate hereditary ovarian cancer. Women at high risk of ovarian cancer could be identified before they get cancer, undergo preventive surgery, and live longer cancer-free lives. For example, some women may have a very high ovarian cancer risk that justifies preventive surgery before menopause, while other women are at increased risk of ovarian cancer later in their lives and could undergo preventive surgery after menopause. The large fraction of ovarian cancer caused by inherited mutations in a variety of genes provides an important opportunity to reduce the incidence and death rate of ovarian cancer, which is a major goal of the Department of Defense s Ovarian Cancer Research Program. Hereditary ovarian cancer disproportionately strikes younger women, leading to many years of life lost. Thus, hereditary ovarian cancer has a major impact on productivity and family life, including those of military families. This proposal will acquire important information to define the hereditary risk of ovarian cancer, which will lead to personalized prevention strategies to save lives of both white and minority women.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510084
Entities
People
- Elizabeth M Swisher
Organizations
- United States Army
- University of Washington