Some women may have gene sequence that reduces breast cancer risk, SFVAMC study finds

Some postmenopausal women carry a gene sequence that may lower their risk of breast cancer, according to new research from San Francisco Veterans Affairs Medical Center. The intriguing results must be repeated and explored further before they will be of practical use in breast cancer medicine, the researchers said.

In the study, about fifteen percent of the women carried a particular sequence in the gene for the growth factor TGF-beta-one. This group also had a 60 percent lower risk of breast cancer, according the paper published in the Wednesday, June 12 issue of the Journal of the American Medical Association.

"It's a really interesting finding, because it fits with previous research in mice that showed TGF-beta might play a role in breast cancer," said lead author Elad Ziv, MD, postdoctoral fellow in general internal medicine at SFVAMC and University of California, San Francisco.

But he cautions that the study does not indicate how the protective effect might work, or whether it could be useful in fighting the disease. "I want to stress that the research is still at the early stages, and we are far away from any applications such as breast cancer tests or treatments," Ziv said.

The researchers studied more than 3000 white, post-menopausal women who had participated in a study on osteoporosis. Using blood samples the women had donated, Ziv and his colleagues generated a DNA sequence for part of the gene for TGF-beta, a protein which inhibits the growth of breast tissue and controls growth of other types of cells.

Artificially increasing TGF-beta levels in mice can protect them against breast tumors, earlier studies have shown.

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 C/C genotype, meaning a cytosine (C) base pair at position 29 on both of their copies of the TGF-beta-one gene, had the higher levels of TGF-beta-one than people with T/C or T/T genotypes, Ziv said.

From this, Ziv and his colleagues hypothesized that women with the C/C genotype might be making more the protein TGF-beta-one, and like the mice could have a lower risk of breast cancer.

In their study, the 458 women in the study with C/C TGF-beta-one genotype had a 60 percent 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, Ziv said.

It's unclear just how the TGF-beta-one genotype might alter breast cancer risk, he said. But the change probably affects the protein's signal region, which tells the cell how to process and route the TGF-beta-one protein, he added.

Much more work is needed to understand the finding, Ziv said. "First, the study should be verified in other populations," he said. Several other genetic links to breast cancer risk have not been verified by further testing.

"We also need to learn whether this protective effect holds true for non-white women and for women before menopause," he said.

Co-authors on the study included Warren Browner, MD, MPH, scientific director at California Pacific Medical Center Research Institute; Jane Cauley, DrPH, professor of epidemiology at University of Pittsburgh; Phillip Morin, PhD, and Robert Saiz, BS, both from Axys Pharmaceuticals, La Jolla, Ca.

The research was supported by grants from the National Institute on Aging (NIA) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

The San Francisco Veterans Affairs Medical Center has been a primary affiliate of University of California, San Francisco since 1974. The UCSF School of Medicine and the SFVAMC collaborate to provide education and training programs for medical students and residents at SFVAMC. SFVAMC maintains full responsibility for patient care and facility management of the medical center. Physicians at SFVAMC are employed by the Department of Veterans Affairs and also hold UCSF faculty appointments.