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Breast Cancer Health Center

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Identifying the Genetic Pathway That Leads to Breast Cancer.

WebMD Health News

Nov. 4, 1999 (Indianapolis) -- Defects in a gene called BRCA1 have been associated with an increased incidence of breast cancer in some women. Research published in the Nov. 5 issue of Science indicates that genetic problems with a protein called ATM may be an important part of the pathway by which BRCA1 mutations lead to breast cancer.

Both BRCA1 and ATM are involved in the repair of DNA when chromosomes are broken, author Stephen J. Elledge, PhD, tells WebMD. Elledge is from the Howard Hughes Medical Institute and the department of biochemistry at the Baylor College of Medicine in Houston. "ATM works as a sensor to see if the DNA is broken, and then it 'tells' BRCA1 if repairs need to be made. ATM functions like the instrument that tells a quality control inspector that something is wrong, and hopefully, the BRCA1 protein fixes it."

Each person has two copies of the gene that are passed down from one generation to the next at conception. If there is a defect on one copy of the gene for ATM, studies have shown that breast cancer is more likely. Two defective copies leads to a disease called ataxia telengiectasia that is almost always fatal by the teen-age years.

The researchers were able to show that the ATM protein was associated with the BRCA1 protein. They then tried to find if the two proteins communicated with each other. Finally, they interfered with this communication and found that BRCA1 would not work properly. Thus, it is important that ATM be able to "talk" to BRCA1 for the latter to do it job properly. The failure to do this may lead to breast cancer in some women.

"We are beginning to understand how the pathways that lead to cancer fit together," says Elledge. "As of now, we only know about two of these genes [BRCA1 and BRCA2], and it is very likely that there are more genes involved that we don't know about. It could be that a significant percentage of breast cancers have to do with problems in this one pathway. With understanding comes the hope of a treatment or even a cure."

Andrew Futreal, PhD, an assistant professor of surgery, obstetrics/gynecology, and genetics at Duke University in Durham, N.C., finds this article to be "provocative but not definitive" in relating BRCA1 to breast cancer.

"This report tells us a little bit more than we knew before about a possible pathway to breast cancer," says Futreal, who was not involved in the study. "Any time we know a little bit more, it puts us a little bit closer to finding a treatment or a cure. "

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