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Closing in on a Prostate Cancer Gene

Susceptibility Locus Identified

For the first time, researchers have found direct evidence that an inherited change can lead to prostate cancer. With about 340,000 new cases diagnosed each year, this disease is the most common cancer in men and is responsible for some 40,000 deaths annually. African-American men suffer the world's highest incidence and death rate for this cancer. Results of the study were published in the November 22, 1996, issue of Science [274, 1371-74).

Scientists at NCHGR, Johns Hopkins University, and Umea University (Umea, Sweden) collaborated in the study involving 91 families, each having at least 3 members with prostate cancer. The team estimates that the faulty chromosomal region accounts for about one-third of hereditary prostate cancers or about 3% of the total number of cases. It may also play a role in other types of prostate cancer that do not have a hereditary component.

The implicated region, on the long arm of chromosome 1 (1q24-25), is now the object of intense scrutiny to identify the responsible gene, already named HPC-1 (hereditary prostate cancer 1). Researchers expect that identification of the gene and its alterations along with elucidation of its function will lead to the development of a susceptibility test and new insights into prevention and management of the disease, which can be treated effectively if discovered early.

Success in finding evidence of a genetic susceptibility came as a surprise to some researchers. "There have been arguments up to the present day that this type of study would be a total failure. Prostate cancer is so common and so complex that finding genes that predispose to the disease was thought to be impossible," said Jeffrey Trent (NCHGR), head of the laboratory that did most of the genotyping.

Another example of such a discovery, noted Trent, is the recent report of a major gene for Parkinson's disease [Science 274, 1197-99 (November 15, 1996)]. "And the same thing has been said about multiple sclerosis, diabetes, schizophrenia, hypertension, and other complex diseases," he continued. "These diseases are so common that in the past geneticists have said we can't address them. But a study like this shows that they really are approachable. And the information we get from them ultimately will be of tremendous benefit to patients."

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