Homing In On a Gene for Prostate Cancer

Scientists have found a small region on a human chromosome harboring a gene that substantially increases the risk of prostate cancer, says a Report in the 22 November issue of Science. Once the gene is identified, it could lead to a test to assess whether a male in a family with a high incidence of prostate cancer has a mutated version that puts him at high risk for the disease.

Molecular biologist Jeffrey Trent of the National Center for Human Genome Research (NCHGR) knew he was taking a big risk when he and collaborators at Johns Hopkins University, the University of Michigan, and Umeå University in Sweden decided to search for a gene for the familial form of prostate cancer. The cancer is very common--striking some 340,000 men each year in the United States alone--but only an estimated 3% of cases are caused by an inherited mutation. This makes it hard to tell whether multiple cases in a family are really due to a susceptibility gene or simple chance. And because prostate cancer usually strikes late in life, the multiple-generation families needed to follow the inheritance of a gene are scarce.

The team drew on a database of 2500 families that seemed to have an elevated prostate cancer risk because they had two or more affected members. The group focused first on 66 families that had at least three males with prostate cancer. They analyzed the genomes of various members of the families for some 341 DNA markers, looking for any variations that were consistently inherited with the prostate cancer--an indication that the markers are located near a susceptibility gene. Their analysis revealed a marker on chromosome 1's long arm that did seem to travel together with cancer risk. Confirmation, and a more precise location of the gene, came when the researchers looked at other chromosome 1 markers in their original 66 families plus another 25.

Because the gene, which will be called HPC1, for hereditary prostate cancer 1, has not yet been cloned, its function is unknown, although there are hints that it might be a cancer-promoting oncogene rather than a tumor suppressor. The research team estimates that the gene they're homing in on is involved in only about a third of hereditary prostate cancer cases, or about 3% of the total. But the gene may also play a role in prostate cancers that don't run in families. Therefore, says molecular biologist Alfred Knudson of the Fox Chase Cancer Center in Philadelphia, the gene could be a "major contributor" to the risk for prostate cancer.