A Most Exciting Discovery:

A Gene That Appears to Pass on the Risk of Prostate Cancer

Categories: Fall 2006

(This article is based upon research information published in Nature Genetics, June 2006. Dr. Catalona is one of the co-authors and his research population from the Northwestern prostate SPORE Pathology Core is one of the US groups studied. This material is adapted for Quest readers.)

A group of scientists and doctors from around the world , including Dr. William J. Catalona, have participated in a study with an Icelandic company, deCode Genetics, to identify genetic risks for prostate cancer.imP1010004 2

The search has resulted in a most exciting discovery and one which will help to focus the future research on causes of prostate cancer.

Before this study, other genes have been identified in a particular family or group as potential risk

Indicators for prostate cancer, but it was not possible to confirm them in other populations.

William B. Isaacs, Phd, a prostate cancer expert at Johns Hopkins University, called the new finding “very exciting” and added that until now “there haven’t really been any clear-cut examples of genes identified by one group and reproduced across multiple study populations.”

This study confirmed the same gene marker, located on chromosome 8q24, in Icelandic men and then men in Sweden and the United States.

Dr. Catalona explained the importance of the study results.

“These findings may be used to develop some of the first clinical genetic tests for prostate cancer susceptibility and aggressiveness. And they may provide fundamental insights into the causes and development of prostate cancer, insights that could help us identify new molecular targets for treatment and prevention.”

Up until this point, the only established risk factors for prostate cancer were age, family history of prostate cancer and ethnic background. (African Americans are 1.6 times more likely to develop prostate cancer, and 2.4 times more likely to die from the disease than European Americans.)

Although genetics is thought to be involved, no studies, up until this one, definitely proved such a connection. This study did show that the genetic variants increased the risk of malignant prostate tumors.

In addition to connecting the genetic marker, 8q24, to the risk of getting prostate cancer, the study looked at whether particular genetic changes within this area were related to aggressive forms of prostate cancer as measured by high Gleason scores.

Although it did appear that these changes might have a stronger association with the more aggressive forms of cancer, the findings were not conclusive.

More research is needed in this area, and Dr. Catalona and his research collaborators are participating in these new studies.

“We are now working with deCode to use frozen tumor samples from carriers of these genetic variants to perform functional studies to determine how they could cause aggressive prostate cancer,” Dr. Catalona said.

This study for an association between the marker on chromosome 8q24 and the risk for prostate cancer was repeated in an African-American case-control group.

In the three groups of European ancestry from Iceland, Sweden and the US, 13% of the general population carried this gene variant. In the African-American group, 30% carried this gene variant.

Carrying this genetic marker raised the risk of getting prostate cancer by 60% compared to men who were not carriers.

deCode Genetics scientist, Laufey Amundadottir, indicated this genetic change accounts for about 8% of prostate cancer cases.

These findings may explain the higher incidence of prostate cancer in African American men than in men of European ancestry.

Finding this genetic marker might provide the information to develop a diagnostic test which would let doctors know which men are most likely to develop an aggressive form of prostate cancer, or at the least a malignant cancer in the prostate. These test results might help doctors decide how closely to follow men at high risk and how to treat prostate cancer cases.

David Altshuler, a medical geneticist at the Broad Institute in Cambridge, Massachusetts explained that because four populations were tested, “It is a model for how these things should be done.”

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