Molecular 'clock' could predict risk for developing breast cancer

“Interestingly, having children, which is known to reduce breast-cancer risk if it occurs early in life, was associated with a reduction in methylation for some genes,” Dr. Euhus said.

Dr. Euhus says the clock is not always marching forward, and there are ways to turn it back.

“Methylation can be stopped or slowed down,” said Dr. Euhus, who also directs the Mary L. Brown Breast Cancer Genetics and Risk Assessment Program at the Harold C. Simmons Comprehensive Cancer Center. “We found that having a baby set the clock backward and so did getting close to menopause. Things that are known to reduce breast-cancer risk may also turn the clock backward.”

A test for methylation of tumor-suppressor genes is not commercially available and Dr. Euhus says additional research is necessary to fully understand the mechanism. For example, it is not clear whether tumor-suppressor gene methylation is simply a marker of prior cell divisions, or whether it can cause increased cell division, hastening the development of breast cancer.

Dr. Euhus said medications that interfere with methylation might provide a new approach for reducing breast-cancer risk.

“Even if there’s a lot of methylation, I can’t tell for sure if a woman is going to develop breast cancer,” Dr. Euhus said. “However, if I took two women from our study and one had more methylation than the other, the one with more methylation was more likely to have already had breast biopsies for benign disease, or had already been diagnosed with breast cancer.”

Measuring tumor-suppressor gene methylation might not work well to predict breast-cancer risk in all women. For women with a strong family history of breast cancer, the concept won’t work because those breast cancers are associated with DNA repair issues and not methylation, Dr. Euhus said.

Dr. Euhus is currently conducting a federally funded study to determine which of the approximately 20,000 to 25,000 genes in the human genome are most strongly associated with breast-cancer risk when methylated. Women interested in participating in this project can contact Florence Kampmeier at 214-648-7039.

Other UT Southwestern authors on the journal paper are Dr. Dawei Bu, a research instructor of surgery; Dr. Sara Milchgrub, clinical professor of pathology; Dr. Xian-Jin Xie, assistant professor of clinical sciences; Aihua Bian, a biostatistical consultant in clinical sciences; Dr. Marilyn Leitch, professor of surgical oncology; and Dr. Cheryl Lewis, a research instructor of surgery.

The research was supported by the American Cancer Society.

Visit http://www.utsouthwestern.org/cancercenter to learn more about UT Southwestern’s clinical services in cancer.

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Dr. David Euhus -- http://www.utsouthwestern.edu/findfac/professional/0,2356,20095,00.html