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 risk.
"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 cancer.
"Since African-Americans have, on average, fewer CAG repeats, it likely contributes to the higher incidence and mortality in this population," he said.