P&S Journal: Winter 1998, Vol.18, No.1
New Gene for Breast Cancer Susceptibility
Mutations in the gene P-TEN can increase a woman's risk of breast cancer, according to a study published in the Nov. 1, 1997, issue of the American Journal of Human Genetics. This breast cancer susceptibility gene joins two others identified: BRCA1 and BRCA2.
The study was a collaboration between Columbia's Dr. Monica Peacocke and Myriad Genetics in Salt Lake City, Utah. The P-TEN gene, also called MMAC1, was discovered simultaneously in February 1997 by researchers at P&S and Myriad Genetics. P-TEN is involved in a wide variety of cancers, including brain, breast, and prostate.
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 mainly affects women, causes skin rashes, tiny wart-like bumps, thyroid disease, and, beginning in the teen-age years, severe benign fibrocystic disease. By the time women reach their 40s, 50 percent to 75 percent of Cowden's syndrome patients 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 of dermatology. Cowden's syndrome also may 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. But this is another piece of the breast cancer puzzle." Dr. Peacocke and colleagues are testing women with a family history of breast cancer and thyroid disease for mutations of P-TEN, which would give an early warning of cancer risk.
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.