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Study shows 1 in 5 women with ovarian cancer has inherited predisposition
Date:1/22/2014

with ovarian cancer in the study did not have known family histories of breast or ovarian cancer or rare cancer syndromes, all of which can increase the odds of developing ovarian tumors. The women ranged in age from 26 to 89, and 90 percent were Caucasian.

The researchers, including Washington University first authors Krishna Kanchi, Kimberly Johnson, PhD, and Charles Lu, PhD, performed a genetic analysis of each woman's tumor and her own DNA, taken from a skin sample. By comparing the genetic sequences side-by-side, they identified the acquired mutations in individual tumor samples. In addition, by comparing the patients' DNA samples with the DNA of 557 women who did not have ovarian cancer and served as controls, the researchers found inherited mutations.

In all, the scientists identified 222 inherited genetic variants that increase the risk of ovarian cancer. Some occurred in genes already known to be associated with a genetic predisposition to ovarian cancer, such as BRCA1 and BRCA2, while others occurred in genes that have never been linked to the disease.

The inherited mutations identified as part of the study involved major genetic changes where large chunks of the protein-coding sequences were truncated, or shortened, disrupting the function of key proteins such as those that normally keep cell division in check or repair mistakes in DNA. The scientists also are working to develop new experimental approaches to verify or rule out whether other, smaller inherited genetic changes they discovered also are linked to the development of ovarian cancer.

"With more research, we expect to find additional mutations linked to hereditary ovarian cancer," Ding said. "Thus, 20 percent is a conservative estimate."

Twenty percent of women with ovarian cancer in the study had inherited mutations in a critical pathway of genes associated with Fanconi anemia, a rare, hereditary bone marrow disease. Genes in this pathway are involve
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Contact: Caroline Arbanas
arbanasc@wustl.edu
314-286-0109
Washington University School of Medicine
Source:Eurekalert  

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Study shows 1 in 5 women with ovarian cancer has inherited predisposition
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