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

By Kevin Boyd

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

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