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Hereditary Prostate Cancer Appears More Aggressive

Hereditary Prostate Cancer Appears More Aggressive

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."

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