AACR 2009: Genetic Variant Associated With Aggressive Prostate Cancer

Zosia Chustecka

April 22, 2009

April 22, 2009 (Denver, Colorado) — One of the biggest issues in prostate cancer is differentiating between men who have aggressive tumors that could be fatal and men who have indolent tumors that might never become clinically significant.

Researchers reporting a new genetic variant associated with aggressive prostate cancer say it could be useful in differentiating between these 2 groups of patients. The finding was reported here at the American Association for Cancer Research (AACR) 100th Annual Meeting in a poster that won an AACR Highly Rated award.

The genetic variant is detected from a blood sample, and it shows a person's predisposition to aggressive prostate cancer, lead author John Wittle, PhD, from the Institute of Human Genetics at the University of California at San Francisco, told Medscape Oncology.

It was found in a case–control study involving 947 men with aggressive prostate cancer and 534 controls, and is located on the KIAA1217 gene, which has recently been reported to be a novel target for repression of the androgen receptor.

This is the first time this has been found, so it needs validation, Dr. Whittle emphasized. Other groups are working to replicate the finding. If it is validated, it could be very important, he said.

The group is now working on a prediction model, in which information on this genetic variant is added to the clinical data that are already used — prostate-specific antigen (PSA) levels, Gleason score, and tumor staging — to see if it can improve accuracy. The hope is that it will, and that it will enable clinicians to identify with more certainty men who are likely to have aggressive disease. This could result in less overtreatment, Dr. Wittle said, because clinicians will be able to identify which tumors will not cause a problem.

Because the marker identifies a predisposition for aggressive disease, it could also be useful in screening for prostate cancer, Dr. Wittle noted, because it would identify those who could benefit from more frequent screening.

Interesting Finding, But Early

"This is a very interesting finding," said Eric Horwitz, MD, acting chair of radiation oncology at the Fox Chase Cancer Center, in Philadelphia, Pennsylvania. Dr. Horwitz specializes in treating prostate cancer, and was approached by Medscape Oncology for comment. The clinical factors that are currently used to predict whether a tumor is aggressive or not are "broad brush" and are sometimes not that accurate, he explained. PSA levels, in particular, can be unreliable; a patient with an aggressive tumor could have low levels, not the high levels that would be expected.

"A test that shows a genetic variant could fill in some of the pieces that are missing from the puzzle," Dr. Horwitz said, and "could potentially provide us with information to differentiate between patients." However, he cautioned that this work is still at the stage of basic research, and has not yet been tested in the clinic.

American Association for Cancer Research (AACR) 100th Annual Meeting: Abstract 87. Presented on April 19, 2009.

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