WASHINGTON--An international team of researchers has mapped a major gene that predisposes men to prostate cancer to the long arm of chromosome 1, finally resolving the question of whether genes for this cancer actually exist. Dubbed HPC-1, for hereditary prostate cancer 1, the gene appears to account for about 3% of the 340,000 prostate cancers diagnosed annually in the United States.
The study involved 91 families in which at least three and as many as 15 first-degree relatives had developed prostate cancer. The new data indicate that approximately 1 man in 500 carries a cancer-disposing alteration in the gene, and that between 200,000 and 300,000 US residents are HPC-1 carriers. A model used by the team estimated that 88% of men who inherit the gene will develop prostate cancer by age 85.
The collaborative effort involved scientists at Johns Hopkins Medical Institutions, the NIH's National Center for Human Genome Research (NCHGR), Umeå University, Sweden, and the University of Michigan. They included Jeffrey M. Trent, PhD, scientific director of the NCHGR; Patrick C. Walsh, MD, and William B. Isaacs, PhD, both of Hopkins; and NCHGR director Francis S. Collins, MD, PhD. Their findings appeared in the Nov. 22, 1996, issue of Science.
Initially, Johns Hopkins researchers analyzed data and tissue samples from 66 high-risk families, all of whom had at least three first-degree relatives with prostate cancer. NCHGR researchers carried out genome-wide scans of DNA from these families, which indicated the gene resided on chromosome 1. An analysis of 25 additional high-risk families, 13 from the United States and 12 from Sweden, confirmed this finding.
Gene hunters are now trying to isolate and sequence the gene, which they expect will provide new insights into hereditary prostate cancers and perhaps the process by which the nonhereditary version occurs. They also are continuing their search for additional prostate cancer genes.
The discovery represents a first step toward clinical applications, a step comparable to the first evidence some 6 years ago for the existence of the breast cancer gene BRCA1, a team member said at a media briefing.
High-Risk Individuals Sought for Study
Dr. Walsh and his colleagues are asking people who have had at least three close relatives diagnosed with prostate cancer to take part in a genetics study of the disease. Interested individuals can call 410-614-5434, or write: Patrick C. Walsh, MD, Hereditary Prostate Cancer Study, Dept. W, Brady Urological Institute, Johns Hopkins University Hospital, Baltimore, MD 21287.