Three areas on chromosomes contain prostate cancer aggressive genes

July 26, 2000

Prostate cancer is the most common cancer among U.S. males. It is the second leading cause of cancer death -- trailing only lung cancer -- in that group. In the year 2000, approximately 180,400 men nationally will be diagnosed with prostate cancer, a disease accounting for about 31,900 deaths annually.

Little is currently known about what makes some prostate cancer biologically aggressive and more likely to progress to metastatic and potentially lethal disease. One compelling possibility is that genetic factors help drive the mechanisms underlying prostate cancer aggressiveness.

Now, for the first time, researchers have taken a direct measure of prostate cancer aggressiveness in a genome-wide scan. The results, which appear in the July issue of the "American Journal of Human Genetics," suggest three candidate regions that give evidence for linkage to prostate cancer aggressive genes. They are located on chromosomes 5q, 7q, and 19q.

"This indicates that one or more of these candidate regions may contain genes that influence the progression of prostate cancer from latent to invasive disease," said John S. Witte, lead author and associate professor of epidemiology and biostatistics at Case Western Reserve University's School of Medicine. "Identifying such genes would be extremely valuable for elucidating the biologic mechanisms underlying prostate cancer progression and for determining treatment in men diagnosed with the disease," he said.

The researchers ranked cancer aggressiveness with the Gleason score, a key pathological measure assigned to a prostate tumor. Gleason score reflects the patterns of tissue architecture observed by a pathologist in two prostate biopsy or surgical samples.

Low Gleason scores indicate that the tumor cells are well differentiated and organized into glandular structures. In contrast, higher scores signify less differentiation of the tumor cells: they appear solid and dissipate together. Poor differentiation, and, hence, a high Gleason score, is a strong prospective gauge of which tumors will penetrate the prostate capsule, invade the seminal vesicles, and spread to the lymph nodes. Therefore, the researchers determined, genes linked to Gleason score -- and hence tissue architecture -- could serve as molecular markers of prostate cancer aggressiveness.

To investigate this possibility, the researchers from CWRU, Washington University in St. Louis, and the Marshfield Medical Research and Education Foundation in Marshfield, Wisconsin, evaluated genetic markers spaced across the genomes of 513 brothers with prostate cancer to determine whether these markers are inherited along with a predisposition to more aggressive disease, as indicated by Gleason score. The researchers found evidence for linkage with Gleason score in three regions on chromosomes 5q, 7q, and 19q.
Other authors were Katrina A. B. Goddard, David V. Conti, Robert C. Elston from CWRU; Jennifer Lin, Brian K. Suarez, and William J. Catalona from Washington University; and Karl W. Broman, James K. Burmester, and James L. Weber from Marshfield.

Case Western Reserve University

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