This gene mutation is found in about 70
percent of African-Americans today, says Alex Lentsch, PhD, of the
Department of Surgery. Dr. Lentsch led the research, presented April 5
at the American Society of Investigative Pathology's Experimental
Biology 2005 conference in San Diego.
The mutation halts the action of a red
blood cell receptor known as the Duffy antigen/receptor for chemokines
(DARC). Chemokines are small proteins that promote angiogenesis (blood
vessel growth)--a function essential for tumor growth.
Originally identified by scientists as
the red blood cell receptor involved in infection by the malarial
parasite, the DARC is now thought to play a role in preventing or
slowing tumor growth.
The DARC receptor--when able to function
properly--is believed to bind to and remove chemokines from a site of
overproduction, such as a tumor.
When the DARC is "knocked out," however,
which is exactly what happened as a result of the anti-malarial genetic
mutation in West African men, chemokines remain active and new blood
vessels are formed, allowing tumors to grow much quicker.
Dr. Lentsch and his research staff bred
mice engineered to develop prostate cancer to those with the DARC gene
knocked out. They were then able to compare the growth and size of
prostate cancer tumors in mice with and without the gene for the DARC.
The mice developed tumors at the same time, but the researchers say this is not surprising.
"Chemokines have not been linked to the
formation of tumors," says Dr. Lentsch. "Once the tumors are formed and
they begin to grow is when the story changes."
In mice bred to have the mutation--those
with the DARC knocked out--tumors grew much faster and were nearly four
times the size of tumors in mice without the mutation. In addition,
researchers noticed higher levels of chemokines in tumors without the
gene for DARC.
These findings, says Dr. Lentsch, could one day be applied to prostate cancer patients.
"Our research shows that prostate cancer
could grow more aggressively in men who have the mutated DARC gene,"
says Dr. Lentsch. "We think this is an important first step to
understanding why African-American men have a 60 percent higher
prevalence of prostate cancer and double the mortality compared with
These preclinical studies will need to be
validated in prostate cancer patients, the researchers add. But once
that is done, a simple blood test measuring the presence or absence of
DARC could be used to identify prostate cancer patients at higher risk
for aggressive tumor growth.
It is also possible that anti-chemokine therapies could be tested and applied to these patients.