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Genetic Marker for Aggressive Prostate Cancer Found
Date:1/11/2010

Variant could be used to guide treatment, researchers suggest

MONDAY, Jan. 11 (HealthDay News) -- A focused search of the entire human genome has found a genetic variant associated with the aggressiveness of prostate cancer, in a discovery that marks an important first step toward singling out cancers that need intensive treatment from those that can simply be left alone.

"It is a proof of principle to show that there are variants in the genome that influence the different kinds of prostate cancer," said Dr. Jianfeng Xu, a professor of epidemiology and cancer biology at Wake Forest University Baptist Medical Center, and leader of a team reporting the finding online in the Jan. 11-15 early edition of the Proceedings of the National Academy of Sciences.

A marker for aggressiveness of prostate cancer is sorely needed, cancer specialists agree. While many men are diagnosed with prostate cancer -- it accounts for one-fourth of all cancer diagnoses in the United States -- a large percentage of those malignancies grow so slowly that they never are life-threatening. Because there is now no way of identifying so-called "indolent" prostate cancers, many men are overtreated, because they and their physicians prefer to be on the safe side.

The new genetic variant cannot be such a marker by itself, Xu said. "One SNP has limited ability, but a panel of SNPs would be useful to identify men who have high risk for aggressive prostate cancers," he said.

An SNP -- single-nucleotide polymorphism -- is a variation in the long string of DNA molecules that make up the genome that determines all human traits.

Xu and his colleagues looked for SNPs in the genomes of 4,829 men with aggressive prostate cancers -- defined as having more disorderly structure and growing beyond the prostate gland -- and 12,205 with slow-growing cancers. They found one SNP that was associated with a 25 percent greater risk of developing aggressive disease.

Several dozen genetic variants have been linked to a greater risk of developing prostate cancer, but this is the first to be associated with aggressiveness of the disease, Xu said.

"The entire field has a long way to go, but this is an important first step," he said.

One indication of the distance to be traveled is the finding that the variant is located in a part of the genome where no gene has been found. This is not an uncommon finding, Xu explained, since many of the risk-associated variants are not in genes. "Our understanding of how the genome works is very limited," he said.

Still, much can be accomplished with what is known, with appropriate changes in strategy, Xu noted. Until now, the focus in prostate cancer has been on finding variants that affect the risk of developing the malignancy. "If you use that approach, it is difficult to distinguish aggressive from non-aggressive cancers," he said. "If you compare two groups of patients, one with indolent disease, one not, you are more likely to find those variants."

A second study comparing the genomes of 1,000 men with aggressive prostate cancer and an equal number with the indolent form of the disease is under way, with results expected to be published later this year, Xu added. The hope is to find a series of variants that might eventually be used by physicians in a screening test to help determine when more than watchful waiting is needed for prostate cancer, he said.

"Our work is too early to say whether it will have a clinical impact," said William B. Isaacs, a professor of urology and oncology at Johns Hopkins Medical Institutions, and a member of the research team. "It wont change the approach to identifying men with the aggressive form of prostate cancer. But this demonstrates that such markers do exist, and by studying them we may be able to understand the biological pathways that contribute to making prostate cancer more aggressive."

"Its not earth-shattering," said William Phelps, program director for translational and preclinical cancer research at the American Cancer Society, "but rather a modest advance over previous genetic analyses, a move in the right direction. Its real importance is trying to focus us on what we can do to develop a protocol to identify aggressive from nonaggressive prostate cancers."

More information

Learn what you need to know about prostate cancer from the U.S. National Cancer Institute.



SOURCES: Jianfeng Xu, M.D., Ph.D., professor, epidemiology and cancer biology, Wake Forest University Baptist Medical Center, Winston-Salem, N.C.; William B. Isaacs, Ph.D., professor, urology and oncology, Johns Hopkins Medical Institutions, Baltimore; William Phelps, Ph.D., program director, translational and preclinical cancer research, American Cancer Society, Atlanta; Jan. 11-15, 2010, Proceedings of the National Academy of Sciences, online


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