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US commercial genetic testing does not detect all cancer-associated mutations in certain genes

Despite a negative (normal) genetic test for mutations in the BRCA1 and BRCA2 genes, about 12 percent of breast cancer patients from high-risk families carried previously undetected cancer-associated mutations, according to a study in the March 22/29 issue of JAMA, a theme issue on women's health.

Co-author Mary-Claire King, Ph.D., of the University of Washington, Seattle, presented the findings of the study today at a JAMA media briefing on women's health in New York.

Inherited mutations in BRCA1 and BRCA2 predispose to high risks of breast and ovarian cancer. Lifetime risks of breast cancer are as high as 80 percent among U.S. women with mutations in these genes, according to background information in the article. Risks for young women with inherited BRCA1 or BRCA2 mutations are particularly increased. Among white women in the U.S., 5 percent to 10 percent of breast cancer cases are due to inherited mutations in BRCA1 and BRCA2. Inherited mutations in other genes, including CHEK2, TP53 and PTEN, can also influence risk of breast cancer.

Clinical options for women at high genetic risk of breast cancer include screening starting at a young age, the use of highly sensitive detection methods, and prophylactic surgeries of the ovaries or breast. Because prophylactic surgeries, while highly effective in reducing risk, are also highly invasive, it is particularly important to distinguish mutation carriers from noncarriers with similarly severe family histories. Women with BRCA1 or BRCA2 mutations are possible candidates for such surgeries. Genetic testing to identify harmful BRCA1 and BRCA2 mutations in as-yet unaffected women with severe family histories of breast or ovarian cancer has become an integral part of clinical practice in many communities. To provide accurate and complete information to high-risk patients, it is critical to understand the implications of a negative test result.

Dr. King and colleagues conducted a study to de
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Contact: Clare Hagerty
206-685-1323
JAMA and Archives Journals
21-Mar-2006


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