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Genetic Mutation Linked to Prostate Cancer
MOST PROSTATE CANCER, says Dr. Timothy Rebbeck,
assistant professor of epidemiology, "just sort of appears out of
nowhere, without any family history." It is, he adds, an "extremely
complex disease," and no single gene or environmental exposure is
going to explain all of it.
But recently, Rebbeck and a team of researchers at Penn's
Cancer Center identified a genetic mutation associated with prostate cancer,
one that could ultimately lead to better prevention strategies. In a study
of 230 Caucasian men with prostate cancer, those who carried a mutation
of the CYP3A4 gene, were diagnosed after the age of 63, and had no family
history of prostate cancer were nearly 10 times as likely to have a higher-stage
(read: worse) tumor than men who did not. The findings were published
in the August 19 issue of the Journal of the National Cancer Institute.
"What the study is essentially saying is that if
you carry this variant, you're much more likely to have a bad tumor, a
worse tumor, than if you don't carry the gene," says Rebbeck, who
served as the study's principal investigator. "The gene essentially
predicts whether you'll have a bad tumor or not."
A lot of men are diagnosed with prostate cancer, he
points out, "and most of those prostate cancers don't go anywhere.
So our ability to identify who's going to have a bad outcome and who isn't
is really important."
Rebbeck's team focused on the CYP3A4 gene because it
processes testosterone through the body -- and because there is a strong
correlation between elevated testosterone levels and the development of
"We think this gene may be involved in regulating
how much testosterone may be available," he says. "Since testosterone
is the fuel that makes prostates grow, how much testosterone you have
hanging around in your system may be very important for whether your prostate
tumor grows or not."
The next steps, he says, are to study the gene more
closely at the molecular level and to conduct a larger study involving
African-American men. "African Americans have the highest rate of
prostate cancer in the world," Rebbeck points out, "and the
genetic variant we found is carried by about 50 percent of African-American
men, compared with only about 10 percent of Caucasian men."
Unlike the HPC1 gene, which has a hereditary link to
prostate cancer but rarely mutates, the CYP3A4 mutation is not believed
to be associated with hereditary prostate cancer. It appears to be associated
with the commonly occurring variety of prostate cancer, which occurs in
older men without a strong family history of the disease. The American
Cancer Society estimates that 184,500 new cases of prostate cancer will
be diagnosed this year in the United States, and that some 39,000 men
will die from it.
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