New Test for Prostate Cancer Risk

June 1, 1996
Oncology NEWS International, Oncology NEWS International Vol 5 No 6, Volume 5, Issue 6

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.

ASCO--Many men diagnosed with prostate cancer will not die oftheir disease if left untreated, but clinicians have no way oftelling which early cancers require more aggressive treatmentand which are likely to be indolent. A new genetic test, developedby researchers at Dana-Farber Cancer Institute, may shed somelight on this important dilemma.

In his ASCO presentation, Dr. Philip Kantoff cited previous researchshowing that a section of the androgen receptor gene has a highlyvariable germline CAG repeat sequence, with the number of repeatsranging from 11 to 33.

Dr. Kantoff, Dr. Edward Giovannucci, and their colleagues determinedCAG repeat lengths in 591 prostate cancer cases and 591 age-matchedcontrols from the Physicians Health Study. They found that shorterCAG repeat lengths correlated with an increased prostate cancerrisk.

"The straightforward explanation is that shorter CAG repeatsin the androgen receptor gene increase the androgen stimulus tothe prostate," Dr. Kantoff said, "and since this isgermline factor, the prostate is exposed to this stimulus constantlyover a lifetime."

For each shortening of the gene section by 6 CAG repeats, therewas 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 behigh grade or high stage," Dr. Kantoff said.

Most important, he noted, length was predictive of those cancersthat were metastatic and fatal. For a decrement of 6 CAG repeats,there was a 2.5-fold increase in the likelihood of metastaticdisease and a twofold increase in the likelihood of lethal prostatecancer.

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

Although the test might someday be used to identify high-riskpatients, Dr. Kantoff cautioned that the data are extremely preliminaryand need validation, and have uncertain implications for men whoalready have prostate cancer.