Scientists find genetic link in cases of prostate cancer 250,000 men in U.S. may harbor a gene that causes disease

November 22, 1996|By Jonathan Bor | Jonathan Bor,SUN STAFF

WASHINGTON -- Scientists said yesterday they have found (( the first conclusive evidence of a gene that causes prostate cancer to run in some families -- sometimes afflicting numerous male relatives within the span of a few decades.

The discovery came after years of detective work by researchers at the Johns Hopkins School of Medicine who, with collaborators elsewhere, combed through DNA from 91 families that have suffered greatly from the disease.

Dr. William B. Isaacs, a Hopkins professor of urology and oncology, said the gene may account for 3 percent of the 340,000 new cases of prostate cancer diagnosed in the United States each year. Those who inherit the gene probably face a 90 percent chance of developing the disease in their lifetime.

Some 250,000 men in the United States may harbor the gene, he said. The gene has been named HPC-1.

"The gene may be active over a wide variety of geographic regions and ethnic backgrounds," said Isaacs, explaining that the study found the trait among Caucasians and African-Americans across the country, as well as men living in Canada and Sweden.

About 10 percent of all cases of prostate cancer are thought to be hereditary, with HPC-1 accounting for about a third of those. At Hopkins, scientists are using a vast trove of family histories to locate the other genes responsible for hereditary cases.

The scientists did not isolate the gene itself. Instead, they found a signpost on the first chromosome that, they believe, sits very close to the gene. Similar discoveries of genetic "markers" have led within a few years to the identification of genes for breast and colon cancer.

"While we don't have the prostate cancer gene, we have the culprit at hand and we know the neighborhood he lives in," said Dr. Jeffrey M. Trent, scientific director of the National Center for Human Genome Research, who collaborated in the study. Identifying the gene "is only a matter of time," he said.

Isolating the gene would mean that doctors would have a test to identify carriers. It could also provide further insights into how healthy prostate cells become diseased ones -- and possibly lead to better treatments.

The discovery was announced yesterday at a news briefing and is described in today's issue of the journal Science. Researchers at Hopkins, the National Institutes of Health and Sweden's Umea University participated in the study.

Elsewhere, scientists who located a hereditary breast cancer gene in 1990 found the gene four years later. Now, research centers are testing women with extensive family histories of breast cancer to see if they carry -- or escaped -- that inheritance.

The search for an inherited prostate cancer gene is being led by Dr. Patrick Walsh, a renowned surgeon who heads Hopkins' Brady Institute of Urology.

Ten years ago, Walsh was impressed by a 49-year-old patient who told him that every close male member of this family -- his father, his father's three brothers and his grandfather -- had died of prostate cancer.

Doctors had long observed that the disease runs in some families. But Walsh was the first to launch a concerted effort to see if such clusters were due to inheritance or to other causes -- such as diet or environment -- and then to look for the culprit genes.

Researchers are still looking for the non-hereditary causes that account for most cases of prostate cancer.

Along the way, Walsh's team found that the risk of developing prostate cancer is much higher for men with family histories of the disease than it is for men with no such history. For instance, men had 11 times the risk if a father and two brothers had been diagnosed.

The prostate is a walnut-sized gland that produces secretions that form part of the seminal fluid in ejaculations. It sits next to the bladder.

Prostate cancer is the most common cancer among men. Some 41,000 men in the United States die of the disease each year, making it the second leading cause of cancer death among men next to lung cancer.

It is usually a disease of older men, striking those who are at least in their 60s. But HPC-1 appears to cause some men to develop the disease earlier -- in some cases, by their 40s.

A genetic test could be of value to men in families that have been hit hard by the disease. Men who are found to carry the gene would have extra incentive to get tested frequently for signs of a tumor. Such tests include a digital rectal examination and a PSA blood test.

Dr. Francis Collins, director of the National Center for Human Genome Research, cautioned that a genetic test, if used widely, could identify 250,000 men who could possibly face discrimination based on their genetic makeup. Insurance companies, for instance, could use genetic information to deny life or health coverage.

Kaiser Permanente researchers recently calculated that women who test positive for a breast cancer gene could cut their death rate by 90 percent if they had their breasts removed. The study sparked concerns that insurers could use the data to push for preventive mastectomies.

Collins also cautioned that the prostate cancer finding does not mean that the disease is diagnosed or treated any differently than before.

Pub Date: 11/22/96

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