Genome Scan
Results
The goal of PROGRESS is to understand why prostate cancer
runs in some families. As you know, we have been collecting blood
samples and family information to look for the location of genes
that may make some families more susceptible to the disease.
The method we are using to search for prostate cancer genes is
called a genome scan. We are looking at many different locations
within the human genome using genetic markers to determine if
men who get prostate cancer share the same pieces of DNA more
often than men who don’t have the disease.
We recently completed our genome scan in the first group of PROGRESS
families. Using 886 DNA samples provided by participants in 94
families, we looked at 380 markers located all across the genome,
resulting in a total of 336,680 pieces of genetic data.
The method we use to analyze this large amount of data is called
linkage analysis. The results of linkage analysis show how likely
it is that two regions of the genome (the marker and the disease
gene) are inherited together, which is represented by a number
called a LOD score. A LOD score greater than three provides evidence
that there may be a susceptibility gene located near that marker.
LOD scores between 1.5 and 3.0 are considered “suggestive”
and additional studies are needed to determine if there is truly
evidence for a susceptibility gene at that location.
Though none of the LOD scores in the total set of 94 families
were above three (the level that would show that the marker may
be close to a prostate cancer gene), we identified six potential
areas of interest located on six different chromosomes. None of
these locations, or loci, has yet been found to contain a gene
for prostate cancer, but it gives us a better idea of where to
focus our search. Our strongest result was on chromosome 11, a
region previously implicated in prostate cancer.
Our genome scan results will be published in the July issue of
the American Journal of Human Genetics. Please contact us if you
would like a copy of the published paper. You may also visit the
journal web site, which has the paper online: http://www.ajhg.org/journal/ |
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A Potential Prostate Cancer Gene on the
X Chromosome
In addition to our genome scan paper, we have a second publication
coming out this summer. The second paper describes results from
our analysis of 186 PROGRESS families at a region called
HPCX.
The HPCX region was first identified in 1998 by a group of researchers
from Johns Hopkins University and the Mayo Clinic along with
scientists from Sweden and Finland. Using linkage analysis,
they identified a place (or locus) on the X chromosome which
appeared to be linked to prostate cancer. We examined the HPCX
region and found very little evidence that this region is linked
to prostate cancer in the families that we studied. Our results
for HPCX may mean that this locus does not account for much
of the prostate cancer occurring in PROGRESS families.
As described above, we are using a genome scan to identify regions
of interest that may contain prostate cancer genes that are
important in our families. Our HPCX results will be published
in the journal Human Heredity. Please contact us if you would
like a copy of the paper when it is published.
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GLOSSARY
OF GENETIC TERMS
Chromosomes: Structures found in every cell nucleus that
store and transmit genetic information. Chromosomes come in pairs.
The human genome consists of 22 pairs of autosomes, numbered 1 through
22, and one pair of sex chromosomes (XX for females, XY for males).
DNA: The substance of heredity. A large molecule that carries
the genetic information or code that cells need to replicate and
to produce proteins.
Gene: A segment of DNA which contains instructions for a
cell to produce a protein.
Human genome: All of the genetic material (genes) in the
23 pairs of human chromosomes.
Genome scan: A technique to find disease-causing genes by
looking for patterns of inheritance at many different genetic markers
(or sign-posts) across the entire genome.
Linkage analysis: A statistical technique to identify markers
which trace patterns of heredity (genes) in families with several
people affected with the disease.
Locus (plural: loci): The position or location on a chromosome
of a particular gene or marker.
LOD (abbreviation for “logarithm of the odds ratio”):
A statistical result that measures the association between a genetic
marker and a potential disease gene.
Marker: A particular sequence of DNA (for which the location
is known), that can be used as an established “landmark”
within the genome to tell where and on which chromosome a gene may
be located.
Susceptibility gene: An inherited (present at birth) segment
of DNA which may contain mutations or important changes in its code
that make an individual more likely to develop a disease or condition. |
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Preventing Prostate Cancer
While we and others are working to understand the genetics of
prostate cancer, researchers are also working on ways to prevent
prostate cancer.
There are two exciting prostate cancer prevention studies being
conducted that may be of interest to you. Both studies are coordinated
by a group of physicians and researchers called the Southwest
Oncology Group (SWOG). The SWOG coordinating center for both studies
is here at Fred Hutchinson Cancer Research Center in Seattle.
The Prostate Cancer Prevention Trial, or PCPT, is a study to
determine if the drug finasteride (also known by the brand name
Proscar) helps to prevent prostate cancer.
Since the study began in 1994, more than 18,000 men have volunteered.
Study participants have been randomly assigned to take either
the drug finasteride or a placebo (an inactive substitute). All
men in the study will take either the drug or the placebo for
seven years. At the end of seven years they will have a prostate
biopsy to see if they have prostate cancer.
If the drug is effective the group of men who take finasteride
will have fewer prostate cancers than the group of men who take
the placebo. It will be several years before the results of the
study are available.
The Selenium and Vitamin E Trial, or SELECT, is a new cancer
prevention study beginning this fall. The goal of this study is
to determine if vitamin E and/or selenium supplements can reduce
the risk of prostate cancer. The researchers are hoping to enroll
more than 32,000 men across North America to participate.
For more information about these prevention trials, and other
cancer research, please contact the Cancer Information Service
at 1-800-422-6237. Canadian citizens may contact the Canadian
Cancer Information Service at 1-888-939-3333.
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Additional
Family Information
We are in the process of expanding our information about
PROGRESS families. As part of this process, we
are now collecting death certificates for certain men
who have passed away. The death certificate will be used
to verify the age at death and cause(s) of death. Written
documentation, such as a death certificate, is very important
for this type of genetic research.
Every death in the U.S. is recorded by the state where
the person died. Some of you may have received a death
certificate information form along with this newsletter.
In order to obtain these records from the Vital Records
office of each state, we need to collect information about
when and where the person died. These details help the
Vital Records staff to locate the documents we request.
When we request these documents from the state, we are
required by federal and state laws to keep all records
confidential.
If you did not receive a death certificate information
form with this newsletter, it means that we already have
the information we need about your family at this time,
or we have sent a request to one of your other participating
relatives. If you did receive a form, please take a moment
to complete the information and mail it back to us in
the envelope provided. The information you provide will
be very helpful to the study. |
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