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Inherited gene change also found in spontaneous tumors

COLUMBUS , Ohio New research shows that a small gene variation that increases the risk of inherited cancer can also arise during the development of spontaneous, or non-inherited, tumors.

The findings, published in the Oct. 5 issue of the Journal of the American Medical Association, suggest that the variation might play a fundamental role in the development and spread of cancer in the body, and that the variant could be an important target for anticancer drugs.

The research focused on the gene for type 1 transforming growth factor-beta receptor, or TGFBR1, and on a variation of that gene, TGFBR1-6A. The 6A variant can be inherited and can increase cancer susceptibility by 19 percent in individuals with one copy of the gene and by 70 percent in those carrying two copies.

The study showed that the 6A variant, which is carried by nearly one in seven Americans generally and by one in six people with cancer, can also arise as a gene mutation during cancer development.

The research was led by scientists at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University .

"Our findings show for the first time that the 6A variation of this gene also arises by mutation during tumor development in patients born with the normal TGFBR1 gene, and that this mutation may contribute to tumor growth and spread," says principal investigator Christopher M. Weghorst, an associate professor with the OSU School of Public Health and a researcher with the Comprehensive Cancer Center.

Furthermore, the researchers found the 6A variant in half of the metastatic liver tumors they examined. These tumors had spread to the liver from the colon.

In some cases, the variants in these tumors had been inherited, but, says lead author Boris Pasche, assistant professor of medicine at Northwestern U
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University
6-Oct-2005


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