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New Regions in DNA Statistically
Associated with Prostate Cancer
Prostate research with sets of brothers revealed genetic
connections with mothers as well as fathers,
an important finding for all families.
Dr. Catalona and his research collaborators have just completed a linkage
analysis of DNA obtained from blood samples collected over ten years from
brothers with prostate cancer.
A linkage analysis is a statistical method to determine if two kinds
of observations or results occur together more often that one would expect
by chance alone.
For example, if all brothers with prostate cancer do not share it, then
the gene probably caused the prostate cancer.
In addition to providing for the development of new blood tests to identify
individuals who are genetically predisposed to prostate cancer, further
research in this are may also provide important insights into preventing
prostate cancer and developing new and more effective treatments for the
disease.
The linkage analysis for this particular research project focused on
pairs of brothers who have the same genetic markers in certain regions
more often than would be expected by chance alone.
The researchers discovered several new regions statistically associated
with prostate cancer. This discovery means that some fraction of
men may carry a mutated gene that predisposes them to prostate cancer.
Previous reports have shown that certain genes in some of these regions
are commonly not present. These "missing" genes are called tumor
suppressor genes. They normally regulate cell growth.
They are like the brakes of a car. When they are deleted, the
car runs out of control. Other genes are like the accelerator of
the car and when they are turned on too much, the car goes out of control.
The study involved 230 sets of brothers (188 pairs, 40trios, and 2 quartets)
for a total of 504 men tested. In total, the analysis involved performing
approximately 209,000 genotypes (DNA tests for variation of genetic markers
which are selected at evenly spaced distances along the length of human
chromosomes).
The researchers divided the brothers into groups according to whether
or not they had a strong family history of prostate cancer, an early or
late age onset of the disease, or had a family history of breast cancer.
These subanalysis discovered a number of other regions in the DNA that
were associated with family history of prostate cancer, age at diagnosis,
and regions that may cause prostate cancer men and breast caner in women.
A genetic connection does exist between prostate and breast cancer.
There are genes that when mutated in men cause prostate cancer and when
mutated in women cause breast cancer. Thus a mother can pass prostate
cancer on to a son and father can pass breast cancer to daughter.
Future studies are being directed at narrowing down these regions to
clone the specific genes involved. Then, studies will be performed
to determine how these genes function normally and how they cause cancer
when they are mutated.
Other doctors participating in this project include Brian Suarez at
Washington University; James Burmester, James Weber, and Karl Broman at
the Marshfield Research Foundation; and John Witte and Robert Elston at
Case Western Reserve University.
(Dr. Catalona and Dr. Suarez have received notice of a department of
defense grant to further support this genetic research.)
Source: Quest, By William J. Catalona, M.D.
and published by the Urological Research Foundation
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