Mutations Linked Breast and Ovarian Cancer Risks

Women with genetic mutations in the BRCA1 and BRCA2 genes have a high risk of breast and ovarian cancer, according to an exhaustive study conducted by researchers at the UW and other institutions.

The New York Breast Cancer Research Group looked at more than a thousand cases, the most extensive study of its kind. Dr. Mary-Claire King, American Cancer Society professor of genome sciences and medicine at the UW School of Medicine, was lead author of the study, which appeared in the Oct. 24, 2003, issue of the journal Science.

Girls who exercise regularly and maintain a normal weight as teenagers might delay the onset of breast cancer in later life.

Health habits also play a role in cancer onset, the study indicated. Women who exercised as adolescents developed breast cancer later in life than those who were not physically active, and those who were not overweight in their teenage years also saw a delay in the onset of the disease.

"It was a surprise, but a source of hope, to learn that factors over which we have some control made a difference in the age at which these highest-risk women developed breast cancer, " King said.

Though family history of breast cancer is still an indicator of risk, about half the women with the mutations who developed breast cancer had no family history of the disease. Most of those women inherited the mutation from their fathers; men are rarely affected by breast cancer.

"So if a family is small, there may be no warning that a mutation is present," King said.

Women carrying the mutations also had a higher risk of ovarian cancer. Those with the BRCA1 mutation had a 54 percent lifetime chance of ovarian cancer, and women with the BRCA2 mutation had a 23 percent chance, compared to a 1.8 percent lifetime risk of ovarian cancer for women in the general population.

Knowing how much more at risk the mutation carriers are for breast and ovarian cancer can help in preventive care methods, King said, such as watching patients more closely for developing tumors, or even having pre-emptive surgery to remove the ovaries because ovarian cancer is so lethal.

Though the genetic mutations in BRCA1 and BRCA2 were linked to breast and ovarian cancer risk in the mid 1990s, that discovery hasn't led to any drug treatments or gene therapies for the diseases.

"Direct gene therapy for cancer is a very hard approach," King explained.

King hopes that further study of the genetic mutations, as well as others linked to cancer, will help find a target gene for some treatment. That gene would have to correspond to a protein that is prevalent in tumors, and not present in normal cells, she said.

King is trying to identify other genetic mutations that increase breast cancer risk, because mutations in BRCA1 and BRCA2 represent only about 10 percent of breast cancer cases.