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CLEVELAND, Nov. 3 /PRNewswire/ -- Researchers at The Cleveland Clinic have discovered a relatively common gene mutation that could double a man's risk for developing prostate cancer.

Results of the study - to be published in an upcoming issue of the journal Nature Genetics - suggest that up to 13% of prostate cancer cases are attributable to a mutation of the RNASEL gene known as R462Q, making R462Q one of the most frequent genetic alterations in any of the common cancers. In comparison, mutations of the widely known BRCA1 gene account for less than 5% of breast and ovarian cancers.

The study was authored by Graham Casey, Ph.D, of the Cleveland Clinic Lerner Research Institute's Department of Cancer Biology; John Witte, Ph.D., of Case Western Reserve University; and a team of collaborating scientists from The Cleveland Clinic, Washington University, and the National Institutes of Health.

Nearly 60% of the 877 men in the study possessed at least one copy of the R462Q variant. Men who inherited only one copy of the mutation from a parent had a 50% increased risk of prostate cancer, while those who inherited two copies of the gene - one from each parent - had a two-fold increased risk of the disease.

"This means that while the effect of carrying the R462Q variant may be relatively small for a given individual, the effect on men's health overall is very large because of the frequency of the R462Q variant in the population," said Dr. Casey. "These findings suggest that screening men for this mutation may be justified in future risk assessment of prostate cancer."

RNASEL is a protein produced by normal cells that can lead to cell death, including the death of cancer cells.  When RNASEL is mutated, one of the brakes to uncontrolled cell growth is removed, which in turn leads to the development of cancer.

Studies from the laboratory of Robert Silverman, Ph.D., of the Cleveland Clinic Lerner Research Institute indicate that the R462Q variant cripples the normal function of RNASEL, but does not stop it from working altogether.  As a result, its effectiveness in preventing uncontrolled cell growth is weakened, thereby increasing the chances of a cell turning cancerous.

In a study published earlier this year in Nature Genetics involving Dr. Silverman and colleagues, the RNASEL gene was associated with increased risk of prostate cancer in families with a history of the disease. In Dr. Casey's study, a specific common alteration in the RNASEL gene was identified as being crucial to increased risk in all men who carry the R462Q variant, not just in those with a family history of prostate cancer.

The study involved collaborative efforts by Drs. Casey and Silverman, Phillippa J. Neville, Ph.D., Sarah J. Plummer, Lisa M. Krumroy, and Ying Xiang, Ph.D., from the Cleveland Clinic Lerner Research Institute; Dr. Witte from Case Western Reserve University; William J. Catalona, M.D., from Washington University; and Nina Nupponen, John D. Carpten, and Jeff Trent from the National Human Genome Research Institute.

The Cleveland Clinic Foundation, founded in 1921, integrates clinical and hospital care with research and education in a private, not-for-profit group practice. Approximately 1,100 full-time salaried physicians at The Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2001, there were more than 2.25 million outpatient visits to The Cleveland Clinic Foundation. Patients came for treatment from every state and from more than 80 countries. There were nearly 52,000 hospital admissions to The Cleveland Clinic in 2001. The Cleveland Clinic website address is www.clevelandclinic.org .

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SOURCE  The Cleveland Clinic  

CO:  Cleveland Clinic Foundation

ST:  Ohio

SU:

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11/03/2002 14:00 EST