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.
Phone: 480.998.0246
Fax:
480.998.0248
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