Prostate Cancer

12-11-2007

PHOENIX, AZ, DECEMBER 11, 2007-Results from two genome-wide association
studies have identified a genetic variant of the DAB2IP gene that is
associated with the risk of aggressive prostate cancer. Research teams from
the Translational Genomics Research Institute (TGen), Wake Forest University
School of Medicine, the Karolinska Institute in Stockholm, Sweden, and Johns
Hopkins Medical Institutions made the discovery jointly.

Researchers suspect that the DAB2IP gene is involved in tumor suppression,
suggesting that this protective mechanism goes awry in men with the variant
form. The finding, reported today in the Journal of the National Cancer
Institute, might one day help doctors tailor treatment based on a patient's
genetic makeup.

Both genetic and environmental factors are important in the development of
prostate cancer, and it is only recently that some of the consistent genetic
factors have been identified. It is not clear at present whether men who are
genetically prone to the disease tend to have more aggressive disease than
men who are not.

"Because there is no way to tell whether a person has or will have the
aggressive version versus the mild version of prostate cancer, both forms
are treated the same-with radiotherapy or surgery to remove the prostate
gland. The identification of this genetic variant could lead to better risk
assessment for aggressive disease, providing doctors with more information
on how to best treat men who may be diagnosed with prostate cancer," said
John Carpten, Ph.D., director of TGen's Division of Integrated Cancer
Genomics and senior author of the paper.

Analysis of 3,159 samples led the researchers to conclude that men
possessing the DAB2IP variant appear to carry a nearly 36 percent increased
risk of advanced prostate cancer.

"In most cases, prostate cancer is not a death sentence, but it would be
ideal to identify men with an aggressive form of disease," said Jianfeng Xu,
M.D., Dr.PH, a senior author and a professor of epidemiology and cancer
biology at Wake Forest University School of Medicine. "Our finding suggests
the possibility of developing a blood test to gauge disease type so doctors
could decide if more aggressive treatment is needed."

The researchers screened DNA samples from 500 men with advanced prostate
cancer and 500 healthy men of the same age in Sweden. This DNA screening
examined the entire genome for more than 550,000 single nucleotide
polymorphisms (SNPs), which are locations on chromosomes where a single unit
of DNA, or genetic material, may vary from one person to the next. The team
then focused on 60,000 SNPs that have also been evaluated by a similar study
conducted by the National Cancer Institute (NCI) called Cancer Genetic
Markers of Susceptibility (CGEMS). Evaluation of these 60,000 SNPs
identified seven SNPs that appeared to be linked to disease aggressiveness.

Additionally, researchers screened another 1,242 men with advanced disease
and 917 healthy men who were part of a research project at Johns Hopkins
Medical Institutions. This group included both African and European
Americans. Through these multiple screenings, the researchers found that the
variant form of DAB2IP is associated with an increased risk of having
aggressive disease.

Senior authors Henrik Gronberg, M.D., Ph.D., a professor of epidemiology
from Karolinska Institute, and William Isaacs, Ph.D., a professor of urology
at Johns Hopkins Medical Institutions, both agree that the findings were
possible because advances in technology allow researchers to take a more
systematic approach to looking at the entire genome. Instead of solely
studying genes that they suspect may be related to disease susceptibility,
they can study the entire genome and look for associations.

"By using state-of-the-art technologies, we can find genes that were not
previously known or thought to be involved with disease risk," said David
Duggan, Ph.D., an Investigator in TGen's Genetic Basis of Human Disease
Division. "If we can then learn more about the proteins they produce, it
could lead to new understanding about disease mechanisms and new
treatments."

Co-first authors on the paper were TGen's Duggan and Siqun Lilly Zheng,
M.D., from Wake Forest.

About TGen
The Translational Genomics Research Institute (TGen), a non-profit 501(c)(3)
organization, is focused on developing earlier diagnoses and smarter
treatments. Translational genomics research is a relatively new field
employing innovative advances arising from the Human Genome Project and
applying them to the development of diagnostics, prognostics and therapies
for cancer, neurological disorders, diabetes and other complex diseases.
TGen's research is based on personalized medicine and the institute plans to
accomplish its goals through robust and disease-focused research.

About Wake Forest University Baptist Medical Center
Wake Forest University Baptist Medical Center is an academic health system
comprised of North Carolina Baptist Hospital and Wake Forest University
Health Sciences, which operates the university's School of Medicine. U.S.
News & World Report ranks Wake Forest University School of Medicine 18th in
family medicine, 20th in geriatrics, 25th in primary care and 41st in
research among the nation's medical schools. It ranks 35th in research
funding by the National Institutes of Health. Almost 150 members of the
medical school faculty are listed in Best Doctors in America.


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