Gene Sequence May Protect Against Breast Cancer

Some postmenopausal women carry a gene sequence that may lower their risk of breast cancer. The intriguing results must be repeated and explored further before they will be of practical use in breast cancer medicine. In the study, about 15% of the women carried particular sequence in the gene for the growth factor TGF-beta-one. This group also had a 60% lower risk of breast cancer according to a paper published in June in the Journal of the American Medical Association. "Itís a really interesting finding, because it fits with previous research in mice", said Elad Ziv, M.D., postdoctoral fellow in general medicine at the San Francisco VA Medical Center and UCSF. He cautions that the study does not indicate how the protective effect might work, or whether it could be useful in fighting the disease. The research is still in very early stages and far away from any applications such as breast cancer tests and treatments.

The researchers studied more than 3000 white, postmenopausal women who had participated in a study on osteoporosis. Using blood samples the women donated, Dr. Ziv and his associates generated a DNA sequence for part of the gene for TGF-beta, a protein that inhibits the growth of breast tissue and controls growth of other types of cells. Earlier studies have shown that artificially increasing TGF-beta levels in mice can protect them against breast tumors. Another previous study showed that people with a particular TGF-beta-one sequence, or genotype, had higher levels of TGF-beta-one. People with a cytosine base pair at position 29 on both of their copies of the TGF-beta-one gene, resulting in a C/C genotype, had higher levels of TGF-beta-one than people with a T/C or T/T genotype. From this it was hypothesized that women with a C/C genotype might be making more of the protein, and like the mice could have a lower risk of breast cancer. The 458 women in the study with C/C TGF-beta-one genotype had a 60% lower risk of breast cancer than women with T/C or T/T. This apparent protection was not related to other risk factors such as estrogen use, age, or number of children.

It is unclear just how the TGF-beta-one genotype might alter breast cancer risk, but the changes probably affect the proteinís signal region, which tells the cell how to process and route the TGF-beta-one protein. Much more work is needed to understand the finding. The study must be verified in other populations, and it will be necessary to see if the protective effect holds true for non-white women and for premenopausal women.