Allele identified that leads to normal values for prostate-specific antigen higher than those for other men
The presence of a certain allele for
a gene controlling prostate-specific antigen levels leads to baseline
values that are roughly 30 percent higher than those of other men,
according to an article in the July 16th issue of the Journal of
the National Cancer Institute.
“Up to 20 percent of men may have genetic
variants that cause levels of prostate-specific antigen that are
about 30 percent higher than other men, which could result in needless
biopsies,” said Scott D. Cramer, Ph.D., lead author of the study.
“Further research will be needed to determine
how this genetic marker can contribute to making prostate-specific
antigen a more accurate screening tool,” said Cramer. “Because of
the huge importance of accurately diagnosing prostate cancer, we
need to find the best way to use prostate-specific antigen to determine
who has prostate cancer and who doesn’t.”
The researchers analyzed blood samples from
405 white males (mean age, 63.7 years) who were part of a study
on asbestos exposure and did not have prostate cancer. With use
of DNA sequencing, the investigators identified 3 regions of variation
in part of the gene that controls blood levels of prostate-specific
antigen. The presence of an allele containing the variant sequences
was associated with a 30-percent increase in baseline blood level.
Further analysis indicated that men with 1 sequence variation have
all 3 variations.
In the study sample of white American men,
roughly 20 percent of the participants had the allele associated
with higher blood levels. Cramer noted that DNA testing for the
allele is both quick and inexpensive; in the future, it might become
part of the screening process to determine a more individualized
‘normal’ range of blood values.
Cramer said additional research should focus
on other racial groups. For instance, black American men are known
to have higher antigen levels and an increased risk for prostate
cancer relative to white Americans. The research by Cramer and colleagues
is the first to identify a specific allele responsible for genetic
differences in antigen levels.
In the U.S., many physicians recommend biopsies
when antigen levels are higher than 4.0 ng/mL. However, there is
considerable controversy about cutoff levels. In the study, antigen
levels ranged from 0.2 to 20 ng/mL. The group of men with the allele
for higher antigen levels had mean levels of 2.0 ng/mL compared
with mean levels of 1.5 ng/mL for the other study participants.
“Prostate-specific antigen has a biological
role in the prostate ? to digest proteins,” said Cramer. “It has
been shown that [the antigen] can process proteins that are important
for prostate growth. One hypothesis is that the higher [antigen]
levels caused by the genetic variants may contribute to prostate
cancer development, which would make testing for the variant even
more important in the screening process.”
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