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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