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In the Laboratory
The laboratories at Fred Hutchinson Cancer Research Center
(FHCRC) and the University of Washington are continuing their
work on the analyses of DNA samples which were submitted by
PROGRESS study subjects. To update you on our progress,
we offer you this brief and simplified explanation of how these
samples are being used to find the genes for prostate cancer.
Each cell in the human body contains in its nucleus 23 pairs
of chromosomes, which contain all the instructions to make and
maintain our bodies. Each chromosome is made up of long strings
of four different "bases" abbreviated A, T, C, and
G that are arranged in pairs. These strings of "base pairs"
are arranged in a certain order to form a code, like letters
or words in a book. There are approximately three billion base
pairs in the human genome. About 10% of this code contains "recipes"
for the cell to produce certain proteins. These sections of
the chromosome which contain instructions to make proteins are
called genes.
To find the genes which may cause prostate cancer in the PROGRESS
families, we are conducting a "genome screen." This
process involves molecular examination of each of the cell's
23 pairs of chromosomes. Because there are billions of base
pairs, it is not possible to look at every one. We look instead
at "marker" regions located about every 10 million
base pairs. The PROGRESS genome screen includes 400 different
markers. We look at each family's DNA, with each marker, to
see if men diagnosed with prostate cancer within a family have
inherited the same particular regions of their genome either
from their mother or father. This is particularly significant
if the patients are diagnosed with prostate cancer early in
life. We compare the data from all the families, looking to
see if affected men in different families share common regions
of their genome. If we find a region that looks significant,
we look at the unaffected men to see if they lack such a region.
For that reason, DNA samples from affected and unaffected men
are equally valuable in our study. Some women in the family
also provide helpful information on genes that occur in the
family.
Once a suspicious area of a chromosome is identified, such
regions become the target of intense study. These regions are
most likely to contain genes which contribute to a man's susceptibility
to prostate cancer. All families in the study are equally valued
in this type of analysis, but larger families and families in
which all invited family members have provided blood samples
tend to provide more data.
In the labs at Fred Hutchinson Cancer Research Center and
the University of Washington, eight scientists are devoting
100% of their time to the genome screen of PROGRESS family
DNA. Thus far, we've gotten some hints about regions of the
genome that may contain prostate genes. Other researchers around
the country are conducting similar studies on different groups
of families. To date, we have screened the entire genome for
70 families, and have screened about one half of the genome
in another 82 families. There are two regions of the genome
that have been suggested by other studies to contain prostate
cancer genes, both on chromosome 1. Detailed analysis of DNA
from the PROGRESS families by Seattle scientists is expected
to help find the exact genomic regions of interest and thus
position researchers to begin closing in on the genes themselves.
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PROGRESS
Data
We have started analyzing information provided on the
PROGRESS questionnaire, which is completed by men with
and men without prostate cancer and selected women in these families.
Based on a review of the questionnaire responses provided by the
first 353 participating men who have not been diagnosed with prostate
cancer, 66.3% report that they have had a PSA blood test done
and 88.7% report that they have had a digital rectal examination
for the early detection of prostate cancer. The average age of
these 353 unaffected men (who have not been diagnosed with prostate
cancer) is 54 years.
The PROGRESS questinonaire also collects information about
family history of cancer. The distribution of prostate cancer
in male relatives of the first 499 men with prostate cancer to
complete and return the questionnaire is summarized in the table
below. To be eligible for the PROGRESS study, a family
must have three or more men diagnosed with prostate cancer. As
shown, a third of the men with prostate cancer report that their
father also had prostate cancer and almost 87% report one or more
brothers diagnosed with the disease. These data and the other
information collected in the PROGRESS questionnaire are
incorporated into our ongoing analyses of the genotyping data
described above. This information will be valuable in our search
for specific genes that cause hereditary prostate cancer. |
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The 1998 Prostate Cancer Facts
Each year the American Cancer Society (ACS) makes projections
about the expected number of new cancer cases and cancer deaths
due to each type of cancer. To obtain a copy of the 1998 Cancer
Facts and Figures, you can call toll free 1-800-ACS-2345 or go
to www.cancer.org on the internet. For 1998, approximately 184,500
men in the United States will be newly diagnosed with prostate
cancer and about 39,200 will die from this disease. For comparison,
the ACS projections indicate that 178,700 women will be newly
diagnosed with breast cancer and that 43,500 will die of breast
cancer in 1998.
Prostate cancer is the most common cancer site in American men.
The incidence (number of newly diagnosed prostate cancer cases
per 100,000 men in the population) of prostate cancer increases
with age. The incidence is higher in African Americans compared
to Caucasian or Asian Americans, and is higher in men with a family
history of the disease. Recent studies suggest that in the general
population about 10% of prostate cancer is due to inherited susceptibility,
but as much as 40% of the disease diagnosed in younger men may
be due to inherited susceptibility. We anticipate that new discoveries
in this area will be forthcoming over the next few years, based
on PROGRESS and other similar studies currently underway.
The early detection of prostate cancer is based on the use of
a blood test called prostate-specific antigen (PSA) and the digital
rectal examination. PSA is an enzyme that is produced by prostate
cells and its level is increased in most men with prostate cancer.
Some increase in the level of PSA can also occur in men with benign
prostatic hyperplasia (BPH), the over-growth of normal prostate
tissue, and prostatitis or infection in the prostate gland.
The American Cancer Society and the American Urology Association
recommend that both the PSA and rectal examination be done each
year beginning at age 50. Men considered to be at higher risk
are those with a strong family history of prostate cancer (for
example, prostate cancer in a father and/or brothers) and African
American men.
For these higher-risk groups, the ACS suggests that early detection
of prostate cancer begin before age 50. The blood samples collected
for PROGRESS are not tested for PSA. If you are interested in
getting a PSA test, check with your doctor about how these guidelines
may apply to you.
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The 1998 Prostate
Cancer Facts
Each year the American Cancer Society (ACS) makes projections
about the expected number of new cancer cases and cancer
deaths due to each type of cancer. To obtain a copy of
the 1998 Cancer Facts and Figures, you can call toll free
1-800-ACS-2345 or go to www.cancer.org on the internet.
For 1998, approximately 184,500 men in the United States
will be newly diagnosed with prostate cancer and about
39,200 will die from this disease. For comparison, the
ACS projections indicate that 178,700 women will be newly
diagnosed with breast cancer and that 43,500 will die
of breast cancer in 1998.
Prostate cancer is the most common cancer site in American
men. The incidence (number of newly diagnosed prostate
cancer cases per 100,000 men in the population) of prostate
cancer increases with age. The incidence is higher in
African Americans compared to Caucasian or Asian Americans,
and is higher in men with a family history of the disease.
Recent studies suggest that in the general population
about 10% of prostate cancer is due to inherited susceptibility,
but as much as 40% of the disease diagnosed in younger
men may be due to inherited susceptibility. We anticipate
that new discoveries in this area will be forthcoming
over the next few years, based on PROGRESS and
other similar studies currently underway.
The early detection of prostate cancer is based on the
use of a blood test called prostate-specific antigen (PSA)
and the digital rectal examination. PSA is an enzyme that
is produced by prostate cells and its level is increased
in most men with prostate cancer. Some increase in the
level of PSA can also occur in men with benign prostatic
hyperplasia (BPH), the over-growth of normal prostate
tissue, and prostatitis or infection in the prostate gland.
The American Cancer Society and the American Urology Association
recommend that both the PSA and rectal examination be
done each year beginning at age 50. Men considered to
be at higher risk are those with a strong family history
of prostate cancer (for example, prostate cancer in a
father and/or brothers) and African American men.
For these higher-risk groups, the ACS suggests that early
detection of prostate cancer begin before age 50. The
blood samples collected for PROGRESS are not tested for
PSA. If you are interested in getting a PSA test, check
with your doctor about how these guidelines may apply
to you.
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