MedicineWorld.Org
Your gateway to the world of medicine
Home
News
Cancer News
About Us
Cancer
Health Professionals
Patients and public
Contact Us
Disclaimer

From Medicineworld.org: Gene Variant May Contribute To Cancer Development

Cancer main Cancer news Breast cancer  

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 his 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 scientists 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 scientists showed that, in the presence of TGF-beta, the growth of cancer cells that carry the TGFBR1*6A gene is 55 percent greater than cancer cells that do not carry this gene, indicating that TGFBR1*6A give cancer cells a selective advantage. This, together with the findings that TGFBR1*6A is acquired by tumors, may explain why half of all liver metastases from colorectal cancer carried the TGFBR1*6A gene while it is only found in 14 percent of the general population.

".individuals who carry the *6A allele, either in the germline or somatically acquired by the tumor, may have a greater likelihood of developing metastases than individuals who do not carry this allele. *6A may therefore serve as a useful biomarker in cancer." The authors add that TGFBR1*6A may bestow cancer cells with a growth advantage in the presence of TGF-beta.

"Since 13.7 percent of the general population and 17.1 percent of patients with a diagnosis of cancer carry at least 1 copy of the *6A allele, our findings may have substantial public health importance. The high frequency of *6A carriers in the general population and the moderately increased risk of breast, colon, and ovary cancer that it confers implies that the dominant effects of *6A have an incomplete penetrance. Additional studies are needed to determine which environmental and genetic factors may modify the penetrance of *6A in these tumor types," the scientists write.

"The results highlight a new facet of TGF-beta signaling in cancer and suggest that TGFBR1*6A may represent a potential therapeutic target in cancer."

JAMA. 2005;294:1634-1646.


Did you know?
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.

Medicineworld.org: Gene Variant May Contribute To Cancer Development

Cancer terms| History of cancer| Imaging techniques| Cancer Main| Bladder cancer news| Cervix cancer news| Colon cancer news| Esophageal cancer news| Gastric cancer news| Health news| Lung cancer news| Breast cancer news| Ovarian cancer news| Cancer news| Pancreatic cancer news| Prostate cancer news| Endometrial cancer news| General info| What is cancer?| Cancer causes| Is cancer hereditary?| Types of cancer| Cancer statistics| Breast cancer main| Breast cancer symptoms| Colon cancer main| Anal cancer| Bladder cancer main| Lung cancer general| Lung cancer main| Non small cell| Small cell| Ovarian cancer main| Treatment of ovarian cancer| Prostate cancer main| Updates in oncology| Acute myeloid leukemia|

Copyright statement
The contents of this web page are protected. Legal action may follow for reproduction of materials without permission.