Genetics of Prostate Cancer: Role of Family History
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Diptasri M. Mandal, Ph.D.
Prostate
Gland and Its Function
The prostate is a male sex gland.
About the size of a walnut and weighing
less than an ounce, the prostate
gland surrounds the urethra, a tube
that transports urine from the bladder
and out of the body. The gland is
located below the bladder and in
front of the rectum. The prostate
gland produces a thick fluid that
forms part of the semen, which nourishes
and helps with transporting sperm.
This gland has two distinct tissue
types: glandular tissue and muscular
tissue. Glandular tissue in the
prostate gland produces the fluid
and the muscular tissue promotes
the male ejaculation.
Cancer
of the Prostate
For a healthy person, cells grow
and divide to produce more cells
when the body needs them. Cancer
of the prostate is caused if the
cells keep dividing when new cells
are not needed. This excess tissue
forms a clump that is called a tumor.
The tumor can be benign (not cancerous)
or malignant (cancerous). In malignant
tumors, cells divide
out of control. They invade and
destroy nearby healthy tissue. If
the cancer spreads from the original
tumor to other areas, it is called metastasic.
Incidence
and Mortality
Prostate cancer is the most frequently
diagnosed malignancy occurring in
as many as 15% of men in the United
States. The American Cancer Society
estimated that during 2005 approximately 232,090 new cases
of prostate cancer will be diagnosed in the United States. It is
the second leading cause of cancer death in men, exceeded only by
lung cancer. The American Cancer Society estimates that 30,350
men in the U.S. will die of this
disease during 2005.
Risk Factors
for Prostate Cancer
A risk factor is anything that increases
a person's chance of developing
a disease. A number of possible
risk factors for the occurrence
of prostate cancer are being actively
explored to understand how these
factors cause cells in the prostate
gland to become cancerous. Some
of the risk factors in prostate
cancer suggested by researchers
are age, race, nationality, diet,
and family history. The only one
possible risk factor that can be
controlled is diet. A diet low in
fat is associated with reduced risk
of prostate cancer. Also, the intake
of lycopene or other compounds in
tomato-based products may reduce
the risk of prostate cancer. The
risk of developing prostate cancer
increases with age. More than 70%
of all prostate cancers are diagnosed
in men over age 65. Race is also
considered to be a major risk factor.
African Americans have the highest
prostate cancer incidence rates
in the world. Interestingly, the
disease is common in North America
and Northwestern Europe and is rare
in Asia, Africa, and South America.
So, diet probably has a major role
to play in the incidence of prostate
cancer.
Importance
of Family History in Prostate Cancer
Recent genetic studies suggest that
hereditary factors may be responsible
for 5%-10% of prostate cancers.
The risk increases in relatives
of affected men. Men with a first
degree relative with prostate cancer
have a two to three fold increase
in risk relative to the general
population. This means that a brother,
father, or son of a prostate cancer
case has a risk of prostate cancer
that is approximately double the
population risk. Male relatives
with two first-degree relatives
have a five-fold increased risk,
whereas, a family history of three
first-degree relatives with prostate
cancer gives rise to an increased
risk of 11-fold in male relatives.
Therefore, relatives with a stronger
family history would be more likely
to have prostate cancer over relatives
of a single case, which means the
more cases in a family the higher
the risk to other male relatives.
Therefore, the familial aggregation
of prostate cancer is useful in
studying the inherited risk to the
disease. In addition, relatives
of early onset cases would have
a higher risk of having prostate
cancer over that of later onset
cases. It was also found that brothers
of cases diagnosed under the age
of 65 had a six-fold increased risk
of developing prostate cancer under
the age of 65 themselves. So, the
three important modifiers of risk
related to familial history of prostate
cancer are: (1) the age of the man
at risk, (2) the age of the affected
relative, and (3) the number of
relatives with prostate cancer.
The following criteria have been
defined for diagnosing hereditary
prostate cancer:
1. a cluster of three or more first-degree relatives with prostate cancer; or
2. prostate cancer in each of three generations in the paternal or maternal lineage; or
3. two or more first- or second-degree relatives with prostate cancer under the age of 55.
Search
for Genes in Prostate Cancer
Recent advances in genetic research
focus on genes linked to hereditary
prostate cancer. Data from independent
studies suggest evidence
for both an autosomal dominant pattern
of inheritance and X-linked or autosomal recessive modes of
inheritance. Males in families with X-linked
or recessive modes of inheritance
for prostate cancer have a higher
risk if they have an affected brother(s)
with prostate cancer than if their
father is affected.
The genetic studies performed to date, mostly on Caucasian families, suggest that seven potential prostate cancer genes are involved in Hereditary Prostate Cancer , which means that genetic risk factors may differ among families. Three of them are located on chromosome 1 (HPC1, PCAP and CAPB) and the other four are located on chromosome 17 (HPC2), chromosome 20 (HPC20), chromosome 8 and the X chromosome (HPCX). Thus far, the search for prostate cancer genes resulted in the identification of three genes (RNASEL at HPC1 region, MSR1 on chromosome 8, ELAC2 at HPC region). However, no single susceptible gene is by itself responsible for a large portion of familial prostate cancers and data were used only from the Caucasian population.
Complexities
in Prostate Cancer Research to Identify
Genes
So far, six potential prostate cancer genes are reported in the
literature. All but HPC2 are yet to be isolated, and they
probably are responsible for only a relatively small proportion
of affected individuals in the general population.
The disease is very
complex due to the existence of
more than one gene and decreased penetrance. (Penetrance is the probability
that an individual carrying a disease
gene is affected. Sometimes an individual
who carries a gene for prostate
cancer may not show symptoms). Moreover,
sporadic and hereditary cases may
co-exist in some families. Thus
far, genetic research studies to
identify genes have been performed
on Caucasian Americans. Interestingly,
confirmatory studies have usually
failed to find the suggested genes
in a different population. A large
number of families from different
populations with family histories
of multiple affected prostate cancer
cases are needed to confirm suggested
genes and to find any new gene that
may exist in the population.
Use
of Genetic Family Study in Prostate
Cancer Prevention
Once the genes are identified, additional
family data are needed for identification
of specific mutations in families
and for determining the penetrances
of different mutations. This information
helps us to estimate an individual's
risk in a family with a history
of prostate cancer. The main problem
associated with the mortality in
prostate cancer is that most of
the time it is diagnosed at an advanced
stage when the cancer is metastasized
to other organs. The detection of
existing genes or finding new genes
will improve the detection and diagnosis
of this cancer at an earlier age
when the cancer is curable. Findings
from genetic family studies will
allow testing to identify men with
specific genetic risk factors, and
this in turn will help with cancer
prevention strategies.
How
to Learn More:
http://www.cancer.org/
http://www.cancer.med.umich.edu/prostcan/genes01.htm
http://www.cancerpage.com/cancers/default.asp?channel=Prostate_Cancer
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