Predicting Prostate Cancer Aggressiveness

Prostate cancer aggressiveness can be predicted with two genetic deletions

(RxWiki News) Genetic defects - mutations, rearrangements, too many copies, etc. - play a role in the development of cancer. Finding these faulty genes can predict risk. Recent research takes risk prediction a step further.

Men who inherit two genetic deletions are much more likely to develop an aggressive form of prostate cancer. Depending on exactly which defects are inherited, the risks can triple or quadruple.

"If prostate cancer runs in your family, find out about genetic testing."

These findings come from an international research effort led by Weill Cornell Medical College investigators.

The team found that one of the genetic deletions affects how another gene functions. The other void found in what's called a "non-coding area of the genome" appears to manage a number of genes.

"We used to think that only genes that made proteins were responsible for disease, but this study shows us that there is inherited information in the non-coding areas of the genome that appear to play a strong role in development of cancer," says study co-author, Dr. Mark A. Rubin, the Homer T Hirst Professor of Oncology in Pathology at Weill Cornell Medical College. 

These findings could be groundbreaking, according to the authors, because it shows that something called "copy number variations" (CNVs) are important in the development of cancer, especially aggressive prostate cancer.

Recent research has linked CNVs with a number of other diseases, including Alzheimer's, mental retardation, autism, Parkinson's, schizophrenia and a form of brain cancer - neuroblastoma.

The two variants don't act alone, says Dr. Francesca Demichelis, who is now an Assistant Professor at the Center of Integrative Biology at the University of Trento in Italy and an Adjunct Assistant Professor in the Institute for Computational Biomedicine at Weill Cornell Medical College. 

"These variants likely collaborate with other factors early in a man's life leading to development of prostate cancer," according to Demichelis.

For this study, researchers studied more than 1900 blood samples from men participating in the Tyrol Early Prostate Cancer Detection Program in Austria. This study has been screening men between the ages of 45 and 75 with prostate-specific antigen (PSA) tests to detect prostate cancer at its earliest stages.

Participants include men with prostate cancer, and men with elevated PSA levels but no cancer. Investigators have also tried to determine why some men with elevated PSA go on to develop prostate cancer and some don't.

The research team discovered two CNVs were very different between the men with aggressive prostate cancer and those without cancer.

These findings were reproduced in a group of 800 patients. The two variants were tested in the lab and found to increase the cancer cell growth and spread.

Researchers are searching for other variants that could help to build a comprehensive DNA test that would allow clinicians to predict how likely a prostate cancer is to grow to an advanced state.

"In this new area of research, we are starting to appreciate that the differences in inherited genomic variants account not only for why we look different or respond in various ways to medication, but also for why we develop disease," Dr. Rubin says.

Results of this research were published in the April 9, 2012 issue the Proceedings of the National Academy of Sciences (PNAS).

This research was supported by the Starr Cancer Consortium, the Early Detection Research Network from the National Cancer Institute, the Clinical and Translational Science Center, the Department of Defense and the National Human Genome Research Institute.

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Review Date: 
April 9, 2012