Stronger Link Found Between ATM Gene and Breast Cancer

City of Hope
Wednesday, 10 September 2003

Finding May Offer Added Tool for Early Detection and Treatment

Scientists at City of Hope Cancer Center and Georgetown University Medical Center, in identifying mutations in the gene that can cause a rare but deadly neurological childhood disease, ataxia-telangiectasia (AT), have found new evidence that the gene also can predispose women to breast cancer.

Called ATM for ataxia-telangiectasia mutated, the altered gene may contribute to about 13 percent of breast cancer, the researchers report in the current issue of the journal Cancer Genetics and Cytogenetics.

The study looked at the DNA of 90 women with early stage (I and II) ductal and lobular breast cancer. "In this study, women with specific alterations in the ATM gene had about a three-fold increased risk of having breast cancer relative to the general population," said Steve Sommer, M.D., Ph.D., director, Department of Molecular Genetics and Molecular Diagnostics, at City of Hope's Beckman Research Institute. He is co-author of the research paper with Anatoly Dritschilo, Ph.D., Georgetown University Medical Center, Washington, D.C.

By comparison, mutations in the better-known BRCA1/BRCA2 gene, which are inherited and occur in five percent of women with breast cancer, contribute a five- to seven-fold increased risk of developing breast cancer during their lifetime.

Dr. Sommer's research goes beyond the initial ATM gene studies, which differed in their conclusions about the ATM gene's role in breast cancer, because the team analyzed ethnically matched women with and without breast cancer. They also used a sensitive gene-scanning method called DOVAM-S, developed by City of Hope researchers, that was able to thoroughly scan the ATM gene, which is called a "monster gene" by scientists for its size.

While only about one in 40,000 Americans has a mutated form of the gene, almost everyone carries two unaltered AT genes, which play an important role in disease prevention.

One of the gene's functions is to sense double-stranded breaks in DNA and start the repair process. DNA damage can cause mutations, which can start and then accelerate the cancer process. A mutation is a change in a gene's DNA sequence, and certain mutations can affect its ability to repair damaged DNA at other places on the chromosomes, resulting in a susceptibility to cancer.

Previous studies of the gene found that while parents of children with A-T never get the disease, they have a predisposition to cancer, and the mothers have a high rate of breast cancer. Dr. Sommers said the continuing scientific detective story is, "Why do children with AT get leukemia and their mothers have a high risk of breast cancer?" Leukemia and breast cancer behave in much different ways.

More than 200,000 U.S. women will develop breast cancer this year, and 40,000 will die of the disease in 2003, according to the American Cancer Society.

Early detection is important to successful treatment of cancer. The next step will be to develop a standard test for the mutated form of the ATM gene to identify high-risk individuals.

The study was funded by a grant from the National Institutes of Health.

The research team also included Zefei Jiang, M.D.; Jinong Feng, M.D.; Carolyn H. Buzin, Ph.D.; Jinong Feng, M.D.; Carolyn H. Buzin, Ph.D.; Jian Zheng, M.D.; Jeffrey Longmate, Ph.D.; all of City of Hope, and Mira Jung, Ph.D. and Jefferson Moulds, Ph.D. of Georgetown University Medical Center.

For more information, or to contact City of Hope, see their website at: www.cityofhope.org