Genetic
Screening of Cancer
Researchers have identified 20 to 30 cancer-susceptibility
genes that greatly increase a person's odds of getting
some form of malignancy. For example, a gene has been
identified on chromosome number 9 that may be linked
to a common skin cancer called basal cell carcinoma.
This gene labeled PTC or patched, may someday be important
in screening for this type of cancer. Another gene,
called HNPCC, is carried by one out of every 300 Americans
and may greatly increase an individual's chance of getting
colon cancer. And the doubly dangerous gene called BRCA-1
seems to give women an 85% chance of developing breast
cancer, as well as a 50% chance of ovarian tumors.
HNPCC
Hereditary nonpolyposis colorectal cancer (HNPCC) is
an autosomal dominant inherited colorectal cancer syndrome
that accounts for 5% to 8% of all colorectal cancers.
Families with HNPCC are at high risk for developing
other cancers, such as endometrial, ovarian, gastric,
small bowel, renal pelvis, and ureter. HNPCC is associated
with germline mutations in mismatch repair genes. MLH1/MSH2
mutations account for 90% of all mutations found in
HNPCC; however, the prevalence of MLH1 and MSH2 mutations
in these families is only about 15% to 60%. Other genes,
notably MSH6, PMS1, and PMS2 have also being described
in a small number of individuals. MSH6 mutations are
commonly associated with atypical HNPCC. Late age of
onset of HNPCC cancers, predominance of endometrial
cancer in female carriers, and microsatellite instability
(MSI) predominantly at mononucleotide repeats with low
penetrance are some of the characteristics of MSH6 mutation
carriers.
MSH2 and MLH1 mutation positive individuals have approximately
a 70% to 90% lifetime risk of developing colorectal
cancer. MSH2 mutation carriers have a higher risk of
developing extracolonic HNPCC cancers, such as endometrial
cancer in women. Studies have validated the usefulness
of these criteria for HNPCC genetic testing.
Even though molecular genetics of HNPCC is still a developing
field, the information available has been used to develop
guidelines for genetic testing and surveillance for
high-risk individuals and families. Identification of
families who are at high-risk enables health care providers
to recommend appropriate screening practices and provide
patients with options of suitable chemoprevention and
prophylactic surgeries. Clinically, genetic testing
is useful to distinguish between high-risk individuals
who need aggressive screening and management and average-risk
individuals whose screening recommendations are the
same as those for the general population.
Benefits of Screening
People with the HNPCC gene mutations have an 80% lifetime
risk of developing colorectal cancer. In 1990, the International
Collaborative Group (ICG) met in Amsterdam and established
the criteria for defining HNPCC families: 1) one family
member diagnosed with colorectal cancer before age 50;
2) two affected generations; 3) three affected relatives,
one of them a first-degree relative of the other two.
Interpreting these test results can be difficult, but
can have the potential to guide a person’s future
medical and lifestyle decisions. It is important for
people to understand the meaning of the results and
also have a clear idea of how they will use these results.
If a HNPCC mutation is identified in an affected family
member, then at-risk family members may choose to undergo
testing for the same mutation. While a positive test
can indicate an increased risk of developing colorectal
cancer, a negative test may not be as informative. A
negative test result does not necessarily indicate freedom
from risk. If a family has a known mutation, a negative
result may mean that a person does not have an inherited
risk; however, it could also mean that current gene
testing is not yet sensitive enough to detect the mutation.
In addition, these individuals could still have a mutation
in one of the other HNPCC genes for which testing is
not yet available.
Individuals with HNPCC tend to develop cancer earlier
in life than those who do not have HNPCC; therefore,
it is recommended that screening in these individuals
begin earlier in life. Because cancers in these individuals
tend to develop more rapidly, the screening procedures
should be performed at shorter intervals to ensure the
greatest chance of detecting the cancer early when it
is most treatable.
Sample required for the analysis
7 ml EDTA blood in special monovettes or vacutainers,
not normal EDTA tubes. When drawing specimen, please
wear gloves and use the tubes which is provided by us.
DO NOT centrifuge and DO
NOT take aliquots for other analysis.
How long and How much
Reports with comments will be delivered within 4-6 weeks
times. Check the Price List
to get the price.
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