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Hereditary Nonpolyposis
Colerectal Cancer (HNPCC)
The majority of colon and rectal cancers are not inherited.
A diet derived mostly from animal sources, a sedentary
lifestyle, age, and a history of chronic inflammatory
bowel diseases are some of the risk factors for the
disease. Still, about 5 percent of colorectal cancer
patients have an inherited form of the disease.
Hereditary nonpolyposis colorectal cancer (HNPCC),
or Lynch syndrome, results in an increased risk of colon
cancer and other cancers—specifically, endometrial
and ovarian cancers in women; gastric cancer; and urinary
tract cancer. Typical of most colorectal cancers, HNPCC
presents few symptoms in early stages. However, one
of the hallmarks of HNPCC is a family history of colorectal
cancer. Diagnosis of HNPCC is sometimes made on whether
the patient meets the Amsterdam Criteria: three or more
family members with colorectal cancer; of the three,
at least one person is a first-degree relative of the
other two and one person was affected before age 50;
colorectal cancer affecting two or more generations;
another type of heritable colon cancer, familial adenomatous
polypsis, is not present; and tumors are verified by
exam.
While the Amsterdam Criteria can be a helpful benchmark,
not everyone who has HNPCC meets the full criteria.
And, the Amsterdam Criteria relies to some extent on
a complete and accurate family history, which may not
always be available.
With HNPCC, there is germline mutation on any of several
mismatch repair genes, whose job it is to prevent DNA
errors during replication: hMLH1, hMSH2, hPMS1, hPMS2,
and hMSH6. People who have inherited an altered mismatch
repair gene have about a 70 percent to 80 percent lifetime
chance of developing colon cancer.
Two types of genetic testing methods for HNPCC are
commonly used: mutation scanning and sequence analysis
and deletion/rearrangement analysis. Mutation scanning
analyzes a segment of DNA to identify variant gene regions,
which are then further studied by sequence analysis,
a determination of the order of base pairs in the segment.
Deletion/rearrangement testing looks for DNA segments
that are missing or out of order.
Genetic testing for HNPCC is not recommended until
an at-risk person is 18, because management of the condition
typically does not begin in childhood. There are, however,
rare, but documented cases of HNPCC affecting younger
people, and for that reason, colorectal cancer screening
is advised to begin 10 years before the earliest age
of onset within a family. For example, if the youngest
relative was 25 when she was diagnosed with colon cancer,
screenings for other family members would recommended
beginning at age 15. In the general population, screening
for colon cancer begins at age 50. Early colorectal
screenings are the best proactive measure for people
with HNPCC, enabling precancerous polyps to be identified
and removed before they progress. Also, HNPCC patients
and their physicians should be aware of their increased
risk for other cancers associated with the condition.
Familial Adenomatous
Polyposis (FAP)
A second type of hereditary colon cancer, familial
adenomatous polyposis, or FAP, involves a mutation of
the adenomatous polyposis coli (APC) gene on chromosome
5.
FAP rarely occurs, but when it does, it is very aggressive.
The APC gene’s role is to control cell growth.
FAP causes hundreds of polyps to grow, often starting
when patients are in their teens. In time, the polyps
become cancerous. If an FAP patient does not seek treatment,
there’s a nearly 100 percent chance he or she
will develop colon cancer by age 45.
There are several genetic tests that can be used for
FAP. Linkage analysis is highly accurate (more than
98 percent) but it can only be used for people who have
more than one FAP-diagnosed family member from different
generations. One of those family members must be willing
to be tested. Another test, full gene sequencing, has
a 90 percent accuracy rate in detecting mutations.
Screening for polyps begins in childhood for people
with FAP. The condition causes so many polyps to grow,
that it is impossible for each polyp to be removed individually.
However, it is essential to the patient’s overall
health to rid the body of polyps before they become
cancerous, so ultimately, removing the colon may be
the only choice. Researchers continue to search for
an effective medical treatment.
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