Download Overview of testing for FAP/AFAP

Testing for FAP/AFAP
Overview of testing for FAP/AFAP
This overview provides detailed information about genetic testing for familial adenomatous
polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP). It is intended to be a
reference for providers. Ordering and interpreting genetic testing may be complex and is best
done by experienced specialists.
When to order genetic testing for FAP/AFAP
Screening for all CRC cases
• Genetic testing for FAP and AFAP is not recommended for all colorectal cancer (CRC)
cases; patients should be tested only if family history and clinical criteria suggest high risk.
Screening for high-risk patients and families
• To confirm a suspected FAP or AFAP diagnosis in a patient (diagnosis made by clinical
criteria), full sequence analysis and/or duplication/deletion analysis of the APC gene
should be performed.
■ Full sequencing appears to be more sensitive than deletion/duplication analysis;
approximately 90 percent of mutations are detected by full sequencing; 8–12 percent
of mutations are detected by deletion/duplication analysis.
• Predictive testing for a high-risk (based on family history) asymptomatic patient requires
prior identification of the disease-causing mutation in the family. Full sequence analysis
and/or duplication/deletion analysis of the APC gene should first be performed on an
affected family member, if possible. If the familial mutation is known, then mutationspecific analysis can be performed on the asymptomatic patient.
■ The same approach can be taken with other high-risk asymptomatic family members
wishing to be tested.
How to interpret genetic testing results
Positive result (mutation identified)
• A mutation identified in the APC gene is diagnostic for FAP or AFAP (each syndrome is
characterized by certain APC mutations).
■ High-risk family members can be tested for the identified mutation
■ Individuals who test positive for the mutation, as well as family members who elect
not to be tested, should follow the surveillance guidelines for FAP/AFAP
■ Family members who are tested and found not to carry the identified mutation
should follow CRC surveillance guidelines for the general population
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Testing for FAP/AFAP
Negative result (no mutation identified)
A negative result (no mutation identified) can be complicated. This result must be interpreted
in the context of a patient’s clinical and family history.
• If there is a known APC gene mutation in the family, then a negative result is
considered a “true negative,” i.e., the patient does not carry the mutation causing FAP or
AFAP in other family members.
■ If the patient is asymptomatic, then he or she should follow CRC surveillance
guidelines for the general population
■ If the patient has clinical symptoms such as cancer or polyps, the disease-causing
mutation is likely sporadic and not within the APC gene; the patient is at increased
cancer risk due to personal cancer history
■ In very rare cases, the patient may carry a different APC mutation than that carried by
other family members
• If there is no known APC gene mutation in the family, a negative result indicates that
an APC disease-causing mutation was not identified. However, this negative result may
be a “false negative,” i.e., there may still be a mutation present, but the method of testing
cannot identify it (test lacks sensitivity), or the testing did not include the APC mutation
responsible for cancer predisposition. This result does not provide useful information for
testing in relatives.
■ If the patient is asymptomatic, a negative result may be a true negative or a false
negative
A true negative means that the patient does not carry a disease-causing APC
mutation (but this cannot be confirmed without knowing what APC mutation is
present in the family)
A false negative can mean any of the following:
• Family may still carry an APC mutation, but patient may not have inherited it
• Method of testing used cannot identify existing mutation
• Testing did not include the APC mutation responsible for cancer
predisposition in the family
Risk is based on clinical and family history
■ If the patient has clinical symptoms such as cancer or colon polyps, a negative result
may be a true negative or a false negative
A true negative indicates that the patient’s symptoms are not caused by an APC
mutation
A false negative can mean any of the following:
• Family may still carry an APC mutation, but patient’s symptoms are not a
result of inheriting it
• Method of testing used cannot identify existing mutation
• Testing did not include the APC mutation responsible for cancer
predisposition in the family
The patient is still at high risk of developing additional cancers and other features
(such as polyps) associated with FAP and AFAP
If an individual has a phenotype like FAP/AFAP, and testing for APC is negative,
consider testing for MYH-associated polyposis (MAP), an autosomal recessive
colon cancer syndrome
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Testing for FAP/AFAP
Variants of uncertain significance (VOUS) in affected or unaffected individuals
• A variation in the normal genetic sequence has been identified, but the causal
relationship, if any, to cancer is uncertain (i.e., it is not clear whether the variation is
harmful)
• Clinical testing of relatives for variants is not recommended
• Patient should remain in contact with the testing health care provider and laboratory in
case new information clarifies the meaning of the test result
• Risks for cancer or cancer recurrence is based on family and clinical history
11-0456:2/12:jt:Updated Feb 2012
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