Gene Hikes Risk of Prostate Cancer

Philadelphia--For the first time, researchers have isolated a gene linked to hereditary prostate cancer. Mutations in the gene, known as HPC2, increase a man's risk of prostate cancer up to threefold, the discoverers said here at the annual meeting of the American Society of Human Genetics on 4 October. The mutations could account for up to 6% of prostate cancer cases, and a test for them could alert at-risk men to be extra vigilant.

Prostate cancer kills about 40,000 men in the United States every year. For years, epidemiologists have known that men with a family history of prostate cancer are more likely to contract the disease. But isolating the genes that transmit this risk has proven difficult, because only about 10% of prostate cancer cases seem to be inherited. Earlier research identified the chromosomal neighborhood where another prostate cancer gene resides, but so far the gene hasn't been pinpointed (ScienceNOW, 21 November 1996).

To isolate the human prostate cancer gene 2 (HPC2), genetic epidemiologist Sean Tavtigian and his colleagues at Myriad Genetics Inc. in Salt Lake City, Utah, studied Utah families, some with histories of prostate cancer. After cloning the HPC2 gene--located on human chromosome 17--from male and female members of each family, the researchers looked for inherited mutations in the gene that appeared in families with high rates of prostate cancer. Tavtigian reported at the meeting the discovery of four mutations in the HPC2 gene that seem to indicate higher risk of developing prostate cancer.

This finding is bolstered by a second study carried out by Tim Rebbeck at the University of Pennsylvania School of Medicine in Philadelphia. In Rebbeck's study, described at the meeting and in the October issue of The American Journal of Human Genetics, researchers collected DNA samples from 359 prostate cancer patients and compared their versions of the HPC2 gene with those of 266 healthy men. Rebbeck found that men who carried two of the mutations identified by Tavtigian were more than twice as likely to have prostate cancer.

Tavtigian's company, Myriad Genetics Inc. in Salt Lake City, Utah, is hoping to develop a test for the HPC2 mutations within a year and a half. However, Rick Kittles of Howard University Medical School in Washington, D.C., cautions that the gene isolated from people in Utah might not be important for other populations. "There's obviously more than one gene [responsible for inherited prostate cancer]," he says, "but we seem to be getting closer" to identifying dangerous mutations.

Related sites
Tavtigian's abstract from the 50th Annual Meeting of the American Society of Human Genetics

Rebbeck's abstract from the ASHG meeting

Tim Rebbeck's Laboratory