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Significant research findings from Michael Milken's CaP CURE funding

Seattle researchers zero in on location of gene for inherited prostate cancer; gene also linked to brain cancer.

SEATTLE ­ Scientists at the Fred Hutchinson Cancer Research Center and the University of Washington have mapped the region of a gene associated with prostate cancer that runs in families. The gene also may trigger an inherited susceptibility to primary brain cancer.
     The study results appear in the American Journal of Human Genetics.
The researchers, who worked three and a half years to map the gene, have named it CAPB, short for "cancer of the prostate and brain." The gene is located on the short arm of chromosome 1 in a region called 1p36.
     "Finding genes such as CAPB may provide clues that will eventually help diagnose, treat, cure and even prevent prostate cancer," says senior author Dr. Elaine Ostrander, head of the Genetics Program at the Hutchinson Center and a UW affiliate professor of molecular biotechnology and zoology.
     Dr. Janet Stanford, an epidemiologist at the Hutchinson Center and at UW, oversaw recruitment of the 141 families nationwide involved in the Prostate Cancer Genetic Study, or PROGRESS.
     "None of this work would have been possible without the participation of these families," says Stanford, a member of the Hutchinson Center's Division of Public Health Sciences and UW research professor of epidemiology.
     Families enrolled in PROGRESS included those with three or more first-degree relatives with prostate cancer, three or more generations affected by prostate cancer and/or two first-degree relatives diagnosed with prostate cancer by age 60.
Participants included men with and without prostate cancer and selected women, all of whom were asked to fill out questionnaires and donate blood samples for DNA analysis.
     Of each family that participated, blood samples were taken from an average of three to four men with prostate cancer. At least a dozen of the families had confirmed cases of both prostate and primary brain cancers.
     Several previous epidemiological studies also have shown an increased risk of brain and central-nervous-system tumors in families with clusters of prostate cancer. These observations led the Seattle researchers to evaluate the possible link between prostate and brain cancers.
     The research is funded by CaP CURE, the Association for the Cure of Cancer of the Prostate, founded by former Wall Street financier Michael Milken.
Dr. Leroy Hood, professor and chair of the UW Department of Molecular Biotechnology, persuaded CaP CURE to donate funds to establish the      Seattle-based Prostate Cancer Genetics Consortium at the UW and the Hutchinson Center. The primary aim of the consortium is to unravel the genetic origins of the disease. CaP CURE now provides more than $2 million a year to this and related projects.
     Blood samples from the PROGRESS family members were processed and frozen at the Hutchinson Center, where they were turned over to Ostrander's group for DNA extraction. Dr. Mark Gibbs from Ostrander's group and Drs. Richard McIndoe and Lisa Chakrabarti from Hood's group performed the genotyping and worked with Dr. Gail Jarvik, a UW mathematical geneticist, to pool the data for linkage analysis.
     "PROGRESS is an outstanding collaboration between the Hutchinson Center and the UW," says Ostrander, also an associate member of the Hutchinson Center's Clinical Research Division. "It works because everyone contributes something unique. This is the future of genetics research."
     The PROGRESS study represents a significant ongoing collaboration between epidemiologists, molecular biologists and geneticists from both institutions.
   "Hood's team leads the field in the development of robotics, high-throughput DNA and protein sequencing systems, and software development to handle the data," Ostrander says. "Using tools of just five years ago, a lab was doing well to complete 250 genotypings a week; PROGRESS has boosted that weekly rate to 15,000."
    The researchers have been aggressive in recruiting families for the study. Many of the families became involved after seeing an appearance on CNN's "Larry King Live" Milken and Gen. Norman Schwarzkopf, who became prostate cancer activists after themselves being diagnosed with the disease. Prostate cancer kills more than 40,000 American men every year.
     While the gene's "neighborhood" has been found, further research is needed to clone the gene and pinpoint its exact "address." The researchers have obtained additional funding from the National Institutes of Health to continue this work. If these findings are confirmed in additional sets of families, the researchers will attempt to clone the gene and discover how it may cause cancers of the prostate and brain.

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Call 1-800-777-3035 for more information

The good news: Scientists at Seattle's Fred Hutchinson Cancer Research Center and the University of Washington have zeroed in on the neighborhood of a gene that appears to cause inherited prostate cancer and primary brain cancer.
    The bad news: Of the nearly 300 families nationwide who have participated in this genetic family study, only a handful have been African American.
    "One limitation of our ongoing research is that we need to enroll more minority families," says Dr. Janet Stanford, the lead investigator in the family identification segment of the Prostate Cancer Genetic Study, or PROGRESS.
     Of 291 families enrolled to date in the PROGRESS study, only six have been non-Caucasian, she says, so the recruitment emphasis in the next few years will involve bolstering participation of minorities, particularly African Americans.
    "Because African Americans have a higher morbidity and mortality from prostate cancer, we think it's important for them to be represented in the study," Stanford says.

African Americans have a 60 percent higher incidence of prostate cancer and a 100 percent higher death rate from the disease as compared with Caucasian Americans.

Researchers seek African-American families with two or more living men who have been diagnosed with prostate cancer, and families of any ethnic or racial background that have five or more men living with prostate cancer.

No travel or expense is required. Volunteers are asked to donate a blood sample and fill out a mail-in health questionnaire. Family members both with and without prostate cancer, including women, may be asked to participate.
All information will be kept strictly confidential.

Those who meet the above criteria are encouraged to call 1-800-777-3035 for more information.

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Kristen Woodward, (206) 667-5095 (FHCRC)
Laurie McHale, (206) 543-3620 (UW)

MARCH 9, 1999

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