Seattle
Researchers Map Gene For Inherited Prostate Cancer
March 1, 1999. 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. 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.
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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AFRICAN-AMERICAN FAMILIES NEEDED FOR ONGOING STUDY OF INHERITED
PROSTATE CANCER
Call 1-800-777-3035 for more information
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.
But 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 twice as high a 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
invited to call 1-800-777-3035 for more information.
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March 11, 1999
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