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Study demonstrates how gene variant may contribute to cancer development

A relatively common cancer susceptibility gene appears to be frequently acquired in metastatic lesions from colorectal cancer, and give cancer cells a growth advantage, according to a study in the October 5 issue of JAMA.

Transforming growth factor beta (TGF-beta) is a potent naturally occurring inhibitor of cell growth, according to background information in the article. It exerts its action by binding to type I (TGFBR1) and type II (TGFBR2) receptors located on the cell membrane. Increased cell growth due to decreased TGF-beta growth inhibition may contribute to cancer development. TGFBR1*6A is a common polymorphism (variation) of TGFBR1. Previous studies have shown that TGFBR1*6A is one of the first candidate tumor susceptibility alleles (DNA codings of the same gene) that is found in a large proportion of the general population (13.7 percent) and significantly increases cancer risk by approximately 24 percent. How TGFBR1*6A contributes to cancer development is largely unknown.

Boris Pasche, M.D., Ph.D., of Northwestern University Feinberg School of Medicine, Chicago, and colleagues conducted a study that included 531 patients with a diagnosis of head and neck cancer, colorectal cancer, or breast cancer recruited from 3 centers in the United States and from 1 center in Spain from June 1, 1994, through June 30, 2004. Multiple genetic testing of the cancer cells was conducted.

The researchers found that TGFBR1 mutated into TGFBR1*6A, i.e. was somatically acquired, in 13 of 44 (29.5 percent) colorectal cancer metastases, in 4 of 157 (2.5 percent) of colorectal tumors, in 4 of 226 (1.8 percent) head and neck primary tumors, and in none of the 104 patients with breast cancer.

While TGF-beta inhibits the growth of normal cells, cancer cells secrete larger amounts of TGF-beta than their normal counterparts. The researchers showed that, in the presence of TGF-beta, the growth of cancer cells that carry the TGFBR1*6A gene is 55 percen
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Contact: Elizabeth Crown
312-503-8928
JAMA and Archives Journals
4-Oct-2005


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