NEW ORLEANS--The inheritance pattern for prostate cancer is becoming
better understood by linkage analysis, and it appears that the inherited
form may be more aggressive than sporadic cancer, according to reports
at the American Urological Association meeting.
Patrick Walsh, MD, presented the work of 22 investigators at three institutions
who have identified linkage to the first hereditary prostate cancer gene
(HPC1), located on the short arm of chromosome 1.
The study used 341 dinucleotide repeat markers to complete a density
map involving 91 families who had at least three first-degree relatives
with prostate cancer. The gene appears to be responsible for one third
to one half of all inherited cases of prostate cancer.
The results showed that men who have an HPC1 mutation are more likely
to be diagnosed with prostate cancer at an earlier age, in a more advanced
state, and with a more poorly differentiated tumor, suggesting that the
gene is responsible for an aggressive form of prostate cancer, said Dr.
Walsh, McConnell Professor and director of urology at Johns Hopkins.
"The characterization of the first hereditary gene is a major finding
in the field," he commented in an interview. "It's the equivalent
of the discovery of the BRCA1 gene for breast cancer."
The NIH-sponsored study included Johns Hopkins, the National Center
for Human Genome Research, and Umeå University in Sweden.
Mayo Clinic Study
More evidence for a gene that conveys a high life-time risk for prostate
cancer was offered by Mayo Clinic investigators. Information about family
history of prostate cancer was obtained from 4,288 prostate cancer patients
and their 17,684 first-degree male relatives.
Daniel J. Schaid, PhD, who presented the data at the AUA meeting, said
that, based on their results, the best-fitting genetic model is autosomal
dominant, with an estimated susceptibility allele frequency of 0.006. Their
model predicts that the cumulative risk of prostate cancer by age 85 is
89% among carriers of the risk allele, and 3% among noncarriers.
For first-degree relatives of the proband, the risk varies according
to the proband's age at diagnosis. If the proband is diagnosed with prostate
cancer before age 60, the risk to first-degree relatives is 34%; between
ages 60 and 70, the risk is 31%; and over age 70, the risk is 17%.
Cleveland Clinic researchers added to the interest in genetics at the
meeting by reporting that men with a family history of the disease had
worse outcome after treatment.
"Men with a family history were significantly more likely to experience
a relapse within five years after undergoing a radical prostatectomy,"
Patrick Kupelian, MD, a radiation oncologist, reported.
The study included 529 men who underwent surgery between 1987 and 1996.
About 12% of the men had a brother or father who had also been diagnosed
with prostate cancer.
Only 46% of the men with family histories remained relapse-free for
five years after prostatectomy, compared with 66% of those without a family
history, Dr. Kupelian said.
"This study suggests that familial prostate cancer is more aggressive
than sporadic prostate cancer," said Eric A. Klein, chief of urologic
oncology at the Cleveland Clinic. "This observation has important
implications for screening men with a family history."