NEW YORK, N.Y., Oct. 31, 1997--Mutations in the gene P-TEN can increase a woman's risk of breast cancer, according to scientists at Columbia University College of Physicians & Surgeons. The findings identify the third breast cancer susceptibility gene; the other two such genes are BRCA1 and BRCA2. The discovery could lead to better tests for early detection and more effective treatments.
The study, published in the Nov. 1 issue of the American Journal of Human Genetics, was a collaboration between Columbia University scientist Dr. Monica Peacocke and Myriad Genetics in Salt Lake City, Utah. The P-TEN gene, also called MMAC1, is located on chromosome 10. The role of this chromosome in the development of various sporadic cancers has been investigated for nearly a decade.
Dr. Peacocke and colleagues made their discovery while searching for the genetic basis of Cowden's syndrome, a little-known dermatological disorder. The autosomal dominant syndrome, which affects mainly women, causes skin rashes, tiny wart-like bumps, thyroid disease, and --beginning in the teen-age years-- severe benign fibrocystic disease. By their 40s, 50 percent to 75 percent of women with Cowden's syndrome develop breast cancer.
"Cowden's syndrome is an under-recognized and under-diagnosed disorder. The identification of this gene will allow us to develop screening tests so that these women can follow early detection and prevention strategies and get prompt treatment of breast cancer," says Dr. Peacocke, associate professor of medicine and dermatology at the Columbia-Presbyterian Medical Center. Cowden's syndrome may also increase a woman's risk of endometrial cancer. Therefore, women with the genetic mutation who also have breast cancer might not be candidates for treatment with tamoxifen, which itself can increase the risk of endometrial cancer.
Researchers are not sure of the exact incidence of Cowden's syndrome. Most cases of breast cancer are the result of sporadic, as opposed to inherited, mutations. "Just as not every woman with breast cancer has mutations in the BRCA1 or BRCA2 genes, not every case of breast cancer will involve P-TEN," says Dr. Peacocke. "But this is another piece of the breast cancer puzzle."
"Based on our finding of P-TEN, we are currently testing women with a family history of breast cancer and thyroid disease for mutations of P-TEN, which would give early warning of cancer risk," says Dr. Peacocke. "This way we can provide more effective genetic counseling for families where there is a significant family history of breast cancer."
The study's other authors were Hui C. Tsou, David H.-F. Teng, Xiao Li Ping, Valeria Brancolini, Thaylon Davis, Rong Hu, Xiao Xun Xie, Alexandra C. Gruener, Carolina A. Schrager, Angela M. Christiano, Charis Eng, Peter Steck, Jurg Ott, and Sean V. Tavtigian.
The study was funded by the National Cancer Institute and the National Institute on Aging.