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Gene linked to
aggressive Prostate Cancer
Newswise — 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., head of TGen’s
Advanced Genomics Technology Lab. “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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