Prostate Cancer Gene Location Narrowed to Chromosome 1 Arm

WASHINGTON--An international team of researchers has mapped a majorgene that predisposes men to prostate cancer to the long arm of chromosome1, finally resolving the question of whether genes for this cancer actuallyexist. Dubbed HPC-1, for hereditary prostate cancer 1, the gene appearsto account for about 3% of the 340,000 prostate cancers diagnosed annuallyin the United States.

The study involved 91 families in which at least three and as many as15 first-degree relatives had developed prostate cancer. The new data indicatethat approximately 1 man in 500 carries a cancer-disposing alteration inthe 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 genewill develop prostate cancer by age 85.

Collaborative Effort

The collaborative effort involved scientists at Johns Hopkins MedicalInstitutions, the NIH's National Center for Human Genome Research (NCHGR),Umeå University, Sweden, and the University of Michigan. They includedJeffrey M. Trent, PhD, scientific director of the NCHGR; Patrick C. Walsh,MD, and William B. Isaacs, PhD, both of Hopkins; and NCHGR director FrancisS. Collins, MD, PhD. Their findings appeared in the Nov. 22, 1996, issueof Science.

Initially, Johns Hopkins researchers analyzed data and tissue samplesfrom 66 high-risk families, all of whom had at least three first-degreerelatives with prostate cancer. NCHGR researchers carried out genome-widescans of DNA from these families, which indicated the gene resided on chromosome1. An analysis of 25 additional high-risk families, 13 from the UnitedStates and 12 from Sweden, confirmed this finding.

Gene hunters are now trying to isolate and sequence the gene, whichthey expect will provide new insights into hereditary prostate cancersand perhaps the process by which the nonhereditary version occurs. Theyalso 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 existenceof 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 leastthree close relatives diagnosed with prostate cancer to take part in agenetics 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.