ASCO--Many men diagnosed with prostate cancer will not die of
their disease if left untreated, but clinicians have no way of
telling which early cancers require more aggressive treatment
and which are likely to be indolent. A new genetic test, developed
by researchers at Dana-Farber Cancer Institute, may shed some
light on this important dilemma.
In his ASCO presentation, Dr. Philip Kantoff cited previous research
showing that a section of the androgen receptor gene has a highly
variable germline CAG repeat sequence, with the number of repeats
ranging from 11 to 33.
Dr. Kantoff, Dr. Edward Giovannucci, and their colleagues determined
CAG repeat lengths in 591 prostate cancer cases and 591 age-matched
controls from the Physicians Health Study. They found that shorter
CAG repeat lengths correlated with an increased prostate cancer
"The straightforward explanation is that shorter CAG repeats
in the androgen receptor gene increase the androgen stimulus to
the prostate," Dr. Kantoff said, "and since this is
germline factor, the prostate is exposed to this stimulus constantly
over a lifetime."
For each shortening of the gene section by 6 CAG repeats, there
was a significant 30% increase in prostate cancer risk and a 70%
increased risk of developing an aggressive prostate cancer. "Interestingly,
the relationship was limited to those cancers considered to be
high grade or high stage," Dr. Kantoff said.
Most important, he noted, length was predictive of those cancers
that were metastatic and fatal. For a decrement of 6 CAG repeats,
there was a 2.5-fold increase in the likelihood of metastatic
disease and a twofold increase in the likelihood of lethal prostate
"Since African-Americans have, on average, fewer CAG repeats,
it likely contributes to the higher incidence and mortality in
this population," he said.