Aug. 21, 1998 A genetic mutation associated with prostate cancer has been identified, for the first time, by scientists at the University of Pennsylvania Cancer Center. The researchers found that men who carry this mutation in the CYP3A4 gene had a more advanced prostate tumor than those without the mutation. These findings are published in the August 19 issue of the Journal of the National Cancer Institute.
"Our results suggest that this gene is involved in prostate cancer," says Timothy Rebbeck, PhD, assistant professor of epidemiology and principal investigator of the study. "This information will lead to more studies that could help us ultimately devise better prostate cancer prevention strategies."
In a study of 230 Caucasian men with prostate cancer, the researchers found that men who were diagnosed after the age of 63, who carried the CYP3A4 genetic mutation, and who had no family history of prostate cancer, were nearly 10 times as likely to have a higher stage tumor than men who did not carry the mutation.
"This discovery has opened up a number of possibilities for further studies. We're getting closer to answering the question of why one person developed the disease instead of another?" says S. Bruce Malkowicz, MD, associate professor of urology and co-collaborator on the study.
The researchers set out to identify genetic mutations that could be used as markers to determine prostate cancer susceptibility. They examined the CYP3A4 gene because one of its functions is to process testosterone through the body and because there is a strong correlation between elevated testosterone levels and the development of prostate cancer. Rebbeck and his colleagues predict that a mutation in the CYP3A4 gene may result in elevated levels of testosterone, thus contributing to prostate cancer development.
The mutation identified in the CYP3A4 gene is not believed to be associated with hereditary prostate cancer, as is the case with the HPC1 gene, which rarely mutates and has a hereditary link. In contrast, CYP3A4 appears to be associated with the commonly occurring variety of prostate cancer in the general population -- that which occurs in older men without a strong family history of the disease.
Prostate cancer is the second leading cancer killer in men. This year, the American Cancer Society estimates that 184,500 new cases of prostate cancer will be diagnosed and approximately 39,000 men will die of this disease in the United States. African-American men are about two times more likely to develop prostate cancer than are Caucasian men. Penn researchers are currently recruiting African-American men for various prostate cancer studies.
The question remains, does a mutated CYP3A4 directly cause prostate cancer?
"That we're still unsure of, and further testing needs to be completed," Rebbeck explains.
"This new information arms us with the knowledge of what can be further investigated," says Malkowicz. "We'll conduct basic science studies attempting to explain a correlation between the mutated gene and the risk of developing prostate cancer."
Drs. Rebbeck and Malkowicz presented the study at the American Urological Association's annual meeting in May and won Michael Milken's CAPCure award for their work.
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