LOCATION OF PROSTATE CANCER GENE FOUND ON CHROMOSOME 1

November 19, 1996
Media Contact: Marc Kusintz
Phone: (410) 955-8665
E-mail: mkusinitz@welchlink.welch.jhu.edu

A team of scientists from the Brady Urological Institute of Johns Hopkins, National Center for Human Genome Research (NCHGR) and Umea University in Sweden have identified the location of the first specific gene that predisposes men to develop prostate cancer. The team has named the gene HPC1 (hereditary prostate cancer 1) and located it on a region of chromosome 1.

Similar to the first step used to locate the BRCA1 gene for breast cancer, now used in genetic testing, the finding is an important step toward developing a genetic test to identify individuals at high risk for prostate cancer, the researchers say. Combined with existing methods to detect early signs of the disease, such a test could lower death rates significantly, they add.

Hopkins researchers previously had shown that 5 to 10 percent of all prostate cancers appear to be inherited; they estimate the HPC-1 gene is responsible for 30 to 40 percent of the hereditary form. More than 40,000 men in the United States die of the disease annually, and African-Americans have the highest incidence and death rates of any population studied. Only skin cancer is a more commonly diagnosed cancer in men.

"This study provides the first strong evidence that specific genes for prostate cancer do exist," says William Isaacs, associate professor of urology and oncology at Hopkins. "And it's a major step toward finding those genes."

The study, published in the Nov. 22 issue of Science, was funded by a National Cancer Institute SPORE grant; The Fund for Research and Progress in Urology, The Johns Hopkins University; Swedish Cancer Society; the Lion's Cancer Foundation at the Department of Oncology, Umea University, and a 1994 CaPCURE award.

To track down the gene, the researchers studied 91 families in which at least three closely related men (for example, father and son or brothers) developed prostate cancer. The team searched the DNA of family members for a region of a particular chromosome that was always inherited by these men. Researchers from Hopkins and NCHGR found such a linkage to a "marker" on chromosome 1. Markers, which like all parts of a chromosome are made up of sequences of DNA, act as "signposts" for a nearby, specific gene.

"This is a monumental advance that could not have been achieved without the dedicated assistance of the families with hereditary prostate cancer, their referring physicians and the scientists working on this project," says co-author Patrick C. Walsh, M.D., urologist-in-chief and director of the Brady Institute.

"Narrowing down our search for a gene to just one small area on a particular chromosome brings us much closer to finding the gene itself," says Henrik Gronberg, M.D., Ph.D., assistant professor of oncology at Umea University and a collaborator in the research at the Brady Institute.

The work done so far narrows the location of the HPC-1 gene to less than 0.1 percent of the human genome--the complete set of chromosomes.

The next goals are to find and clone the HPC-1 gene and to continue the search for other prostate cancer genes. Hopkins researchers are asking that families with three or more affected members contact the study team at (410) 614-5434.

Because they have not yet identified the exact gene, the investigators caution that there is no way at this time to test for the gene in any individual.

Other authors of the study include Jeffrey R. Smith, John Carpten, Michael Brownstein, Jennifer Walker-Daniels, Olli P. Kallioniemi, Joan Bailey-Wilson, Francis Collins, Jeffrey Trent (NCHGR); Diha Freije, Sarah Isaacs, G. Steven Bova, Hong Guo, Piroska Bujnovszky, Deborah R. Nusskern, Jianfeng Xu, Terri H. Beaty and Deborah A. Meyers (Johns Hopkins); and Monika Emanuelsson, Anders Bergh and Jan-Eric Damber (Umea University, Umea, Sweden).



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