Genetic
Testing For Breast And Ovarian Cancer Risk
Learning More,
Making Decisions
Genetic testing is
a process for determining genetic alterations that may be linked
with an increased risk of breast and ovarian cancer.
Genetic testing may
reveal whether the cancer risk in a family is passed through its
genes.
The National
Cancer Institute (NCI) states that there can be benefits
to genetic testing, whether a person receives a positive or
a negative result.
The potential benefits
of a negative result include a sense of relief and elimination
of the need for special preventive checkups, tests, or surgeries.
A positive test result
can bring relief from uncertainty and allow people to make informed
decisions about their future, including taking steps to reduce
cancer risk.
In addition, many
people are able to participate in medical research that may,
in the long run, decrease the risk of death from breast cancer,
according to the NCI.
Genetic testing for
breast and ovarian cancer risk involves looking for altered
genes such as BRCA1 and BRCA2. Although the lab test
is quite complex, only a blood sample is needed.
If a woman is
at increased risk for breast or ovarian cancer, she can
make choices that may help reduce her risk of getting cancer
or help find cancer early.
Cancers develop due
to alterations (mutations) in genes. When an alteration or mutation
in a gene is present in the eggs and sperm, also called germ
cells, it is referred to as a “germline mutation.”
When a germline mutation is inherited it is present in all body
cells.
Only a small percentage
of cancers involve inherited mutations that are passed from
generation to generation.
The majority of cancers
can be attributed to "acquired" mutations. Acquired means that
the mutations occur only in the tissue that is affected by cancer
and are not present in all cells of the body. Acquired mutations
are not inherited and are not passed down to children.
In fact, all people
have altered forms of some genes, according to the NCI.
Some alterations can increase risk for certain illnesses such
as cancer. In recent years, gene alterations have been found
in some families with a history of breast cancer. Some women
in these families also have had ovarian cancer.
Hereditary
Breast Ovarian Cancer Syndrome
Hereditary breast
ovarian cancer (HBOC) syndrome is characterized by the following
features in a family:
-
an early age of onset of
breast cancer (often before age 50)
-
family history of both breast
and ovarian cancer
-
increased chance of bilateral
cancers (cancer that develop in both breasts, or both
ovaries, independently) or an individual with both breast
and ovarian cancer
-
an autosomal dominant pattern
of inheritance (vertical transmission through either the
mother or father’s side of the family)
-
an increased incidence of
tumors of other specific organs, such as the prostate
Other factors that
increase the chance that a family has the hereditary breast
ovarian cancer syndrome include family history of male breast
cancer and Ashkenazi Jewish ancestry.
BRCA1 and
BRCA2 Genes
In 1990, DNA linkage
studies on large families with the above characteristics identified
the first gene associated with breast cancer.
Scientists named this
gene “breast cancer 1” or BRCA1 (pronounced brak-uh).
BRCA1 is located on chromosome 17.
Mutations in the gene
are transmitted in an autosomal dominant pattern (a gene on
one of the first 22 pairs of chromosomes, which, when present
in one copy, causes a trait or disease to be expressed) in a
family.
Since it was clear
that not all breast cancer families were linked to BRCA1, studies
continued and in 1994, scientists discovered another gene (similar
to BRCA1), and named it BRCA2.
BRCA2 is located on
chromosome 13. Mutations in this gene are also transmitted in
an autosomal dominant pattern in a family.
Both BRCA1 and BRCA2
are tumor suppressor genes that usually have the job of controlling
cell growth and cell death. Everyone has two BRCA1 (one on each
chromosome #17) and two BRCA2 genes (one on each chromosome
#13).
When a person has
one altered or mutated copy of either the BRCA1 or BRCA2 gene,
their risk for various types of cancer increases.
The following are
facts about BRCA1 mutations:
-
36 percent to 85 percent
lifetime risk for breast cancer
-
40 percent to 60 percent
lifetime risk for second breast cancer (not reappearance
of first tumor)
-
20 percent to 60 percent
lifetime risk for ovarian cancer
-
increased risk for other
cancer types, such as prostate cancer
The following are
facts on BRCA2 mutations:
-
36 percent to 85 percent
lifetime risk for breast cancer (in females)
-
6 percent lifetime risk for
breast cancer (in males)
-
up to 27 percent lifetime
risk for ovarian cancer
-
increased risk for other
cancer types, such as pancreatic, prostate, laryngeal,
stomach cancer, and melanoma
Both copies of a tumor
suppressor gene must be altered or mutated before a person will
develop cancer.
In HBOC, the first
mutation is inherited from either the mother or father and is
therefore present in all cells of the body.
This is called a germline
mutation. Whether a person who has a germline mutation will
develop cancer and where the cancer(s) will develop depends
upon where (which cell type) the second mutation occurs.
For example, if the
second mutation is in the ovary, then ovarian cancer may develop.
If it is in the breast, breast cancer may develop. The process
of tumor development actually requires mutations in multiple
growth control genes.
Loss of both copies
of BRCA1 or BRCA2 is just the first step in the process. What
causes these additional mutations to be acquired is unknown.
Possible causes include chemical, physical, or biological environmental
exposures, or chance errors in cell replication.
Some individuals who
have inherited a germline BRCA1 or BRCA2 mutation never develop
cancer because they never get the second mutation necessary
to knock out the function of the gene and start the process
of tumor formation.
This can make the
cancer appear to skip generations in a family, when, in reality,
the mutation is present. Persons with a mutation, regardless
of whether they develop cancer, however, have a 50/50 chance
to pass the mutation on to the next generation.
It is also important
to remember that the BRCA1 and BRCA2 genes are not located on
the sex chromosomes. Therefore, mutations can be inherited from
the mother or the father’s side of the family.
Always consult your
physician for more information.
Online
Resources
(Our Organization
is not responsible for the content of Internet sites.)
American
Cancer Society
American
Society for Clinical Oncology
Centers
for Disease Control and Prevention (CDC)
National
Cancer Institute
National
Institutes of Health (NIH)
National
Women's Health Information Center
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April 2004
Genetic
Testing For Breast And Ovarian Cancer Risk
Hereditary
Breast Ovarian Cancer Syndrome
BRCA1
and BRCA2 Genes
Statistics
for Breast and Ovarian Cancer
Testing
Pluses and Minuses
Questions
to Ask About Genetic Testing
Online
Resources
Statistics
for Breast and Ovarian Cancer
According to estimates
of lifetime risk from the National Cancer Institute
(NCI), about 13 percent (132 out of 1,000 individuals)
of women in the general population will develop breast cancer,
compared with estimates of 36 to 85 percent (360 to 850 out
of 1,000) of women with an altered BRCA1 or BRCA2 gene.
In other words, women
with an altered BRCA1 or BRCA2 gene are three to seven
times more likely to develop breast cancer than women without
alterations in those genes.
Lifetime risk estimates
of ovarian cancer for women in the general population indicate
that 1.7 percent (17 out of 1,000) will get ovarian cancer,
compared with 16 percent to 60 percent (160 to 600 out of 1,000)
of women with altered BRCA1 or BRCA2 genes.
A woman’s lifetime
chance of developing breast and/or ovarian cancer is greatly
increased if she inherits an altered BRCA1 or BRCA2 gene.
Women with an inherited
alteration in one of these genes have an increased risk of developing
these cancers at a young age (before menopause), and often have
multiple close family members with the disease. These women
may also have an increased chance of developing colon cancer.
Men with an altered
BRCA1 or BRCA2 gene also have an increased risk of breast cancer
(primarily if the alteration is in BRCA2), and possibly prostate
cancer.
Testing
Pluses and Minuses
The National
Cancer Institute (NCI) suggests that genetic testing
may help a woman:
-
make medical and lifestyle
choices
-
find out that the altered
gene is not present
-
-
decide whether or not to
have prophylactic surgery
-
give other family members
useful information (if a woman chooses to share
test results)
-
There are also disadvantages
to testing, according to the NCI:
-
there is no proven way to
reduce cancer risk
-
there is no guarantee that
test results will remain private
-
a woman may face
discrimination for health insurance, life insurance, or
employment
-
a woman may find
it harder to cope with a cancer risk knowing the
test results
-
negative test results may
provide a false sense of security because a woman thinks
she has no chance of getting cancer, which is not true. She
would still have the same risk as women in the general
population.
-
genetic testing can affect
relationships with family members. A woman should
think about who in her family might want to know
your test results, and whom she might want to tell.
A woman will need
to decide what the advantages and disadvantages of testing are
for her. What is right for one person is not always right for
another.
Always consult your
physician for more information.
Questions
to Ask About Genetic Testing
If a woman is
considering genetic testing, she should discuss this with her physician or genetic
counselor. The following questions are provided by the National
Cancer Institute (NCI):
-
What are the chances that
a gene alteration is involved in the cancer in my family?
-
What are my chances of having
an altered gene?
-
Besides altered BRCA1 or
BRCA2 genes, what are other risk factors for breast and
ovarian cancer?
-
Are all genetic tests the
same?
-
How much does the test cost?
-
How long will it take to
get my results?
-
What are the possible results
of the test?
-
What would a positive result
mean for me?
-
What would a negative result
mean for me?
-
How might a positive test
result affect my health insurance? life insurance? employment?
-
Do I want to submit my test
results to an insurance company? If yes, will they pay
for the testing?
-
Where will my test results
be placed/recorded? How might this affect me? Who will
have access to them?
-
Will having the test do anything
to make me change my current health practices?
-
What are my reasons for wanting
to be tested?
-
What type of cancer screening
would be recommended if I don't get tested?
Always consult your
physician for more information.
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