Researchers at the Johns Hopkins Brady
Urological Institute, Wake Forest University and the
Karolinska Institute in Sweden have identified an array of
gene markers for hereditary prostate
cancer that, along with family history for the disease,
appear to raise risk to more than nine times
that of men without such markers.
Using the panel, gleaned from a study of more than
4,000 Swedes, researchers found that
these markers are common and could account for nearly half
the prostate cancer cases in this study.
Results are published online in the Jan. 16 edition of
the New England Journal of Medicine.
The international research team plans to sample DNA
from U.S. populations of men to
determine if these genetic changes prevail outside of
Sweden. And they caution that the panel of
markers cannot tell how aggressive a potential cancer may
be.
"This information is not yet available as a genetic
test for risk of prostate cancer, but efforts
are under way to rapidly develop one," said William B.
Isaacs, of the Johns Hopkins Brady Urological
Institute, who participated in the study.
"While these findings need to be validated and
refined, it's a step in the right direction to
revealing the genetic-based reasons for this cancer that we
have been looking for over the past 15
years," he added.
In the study, the scientists drew blood from 2,893
prostate cancer patients and 1,781 men
without the disease. White blood cells are a good source of
DNA with which an individual is born, as
opposed to DNA in cancer cells that gets altered by the
environment or other means, according to the
scientists.
Using DNA from blood cells, they sifted through
variations in chemicals called nucleotides that
pair up to form the rungs of a DNA ladder that carries
genetic instructions. These so-called "single
nucleotide polymorphisms," or SNPs, occur when one chemical
base pair is swapped for another,
altering the information in the DNA alphabet or
sequence.
Investigators found 16 SNPs in five different regions
of human chromosomes 8 and 17 that
were more common to men with prostate cancer than those
without the disease. The individual
changes were ones previously linked to prostate cancer and
other diseases, a good indication, the
scientists say, that they were on the right track.
To create their panel, the scientists chose the best
SNPs from each of the five regions and
tested their cumulative effect on prostate cancer risk. As
the number of associated SNPs increased,
so did risk. Men with four or more of these SNPs were
nearly 4.5 times more likely to have prostate
cancer.
"This work strongly suggests that because of the
combination of polymorphisms we inherit, one
man may be more on the path to developing prostate cancer
than another," said Isaacs, who is the
William Thomas Gerrard, Mario Anthony Duhon and Jennifer
and John Chalsty Professor of Urology at
the Brady Urological Institute and professor of oncology at
the
Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins.
Add to that a family history of prostate cancer, and
the risk doubles. Men with all five SNPs
plus a family history of prostate cancer were nearly 9.5
times more likely to have the disease. Further
analysis revealed that 46 percent of prostate cancer cases
in this population were due to these risk
factors. But the scientists estimate that almost 90 percent
of the Swedish population carries one or
more of the five SNPs, elevating their risk for prostate
cancer relative to men who carry none of
these factors.
Swedish populations are relatively homo-genous,
tending to marry other Swedes, and well-suited
for such genetic studies because genetic variation is
somewhat more limited than in larger,
heterogenous groups. Socialized medicine in Sweden also
enables access to robust registries of
patient data.
In addition, Swedes suffer from higher-grade prostate
and other cancers, and deaths among
their Caucasian populations are 10 percent to 20 percent
higher than among American Caucasians,
according to Henrik Gronberg, professor of epidemiology at
the Karolinska Institute and a co-
investigator on the study.
Isaacs and his team note that the SNPs may not in
themselves lead to increased cancer risk but
could be markers linked to other changes that do so.
The Wake Forest and Johns Hopkins schools of medicine
have filed patent applications for the
technology and results described in this study.
Funding was provided by the National Cancer Institute,
Department of Defense, Swedish
Cancer Society and Swedish Academy of Sciences.
GO TO