Colon Cancer and Genetic Testing
Medical Author: Jay W. Marks, MD
Medical Editor: Michael Lill, MD
There has been much excitement during the past decade because of the
identification of abnormal or defective genes (mutations) associated with
in families where colon cancer is common. When a defective gene can be
identified, it is possible to examine other members of the family to see if they
also carry the defective gene. Those individuals who carry the defective gene
are at a very high risk (75%-100%) for developing colon cancer. The reason for
the excitement is that if an individual is found to have the defective gene, his
or her colon can be carefully monitored and then removed before the cancer occurs.
Only 5% of all colon cancers occur in families with a history of colon cancer
and identifiable genetic defects. Therefore, genetic testing as it exists today
is useful for only a minority of the 130,000 people each year who are destined
to develop colon cancer. Nevertheless, genetic testing is important because the
risk is so extremely high among individuals who are found to have the genetic
defect. In addition, more defective genes are likely to be found during the next
few years, and this will make genetic testing valuable for an increasing number
of individuals who will develop colon cancer.
At present, there are two types of familial colon cancer in which defective
genes can be identified. One type of cancer is associated with a strong family
history of colon polyps. The other type of colon cancer is not associated with a
family history of colon polyps. The polyp-associated cancerous disease is called
familial adenomatous polyposis (FAP). (Adenomatous polyps are a type of polyp
that have the potential to become cancerous.) The nonpolyp-associated cancerous
disease is called hereditary nonpolyposis colorectal cancer (HNPCC).
How does someone know if he or she may be a member of a family with FAP and
may need genetic testing?
An individual is likely to belong to a family with FAP if he or she has more
than 100 adenomatous colon polyps or is a first-degree relative (parent,
sibling, or child) of a person who has more than 100 adenomatous colon polyps.
The number of polyps is less in some families, a condition referred to as
attenuated FAP. Therefore, individuals who have between 20 and 100 adenomatous
colon polyps or are first-degree relatives of individuals with 20 to100
adenomatous colon polyps also may belong to a family with FAP.
How does someone know if he or she may be a member of a family with HNPCC and
may need genetic testing?
An individual is likely to belong to a family with HNPCC and require genetic
testing if (1) three or more relatives have had colon cancer (or another cancer
associated with HNPCC such as uterine, small bowel, urethral, or renal pelvic
cancer) and at least one of the relatives is a first-degree relative, (2) two or
more generations of the family have colon cancer, or (3) one or more relatives
were diagnosed with colon cancer before age 50. These criteria for identifying HNPCC are referred to as the Amsterdam II Criteria. The Amsterdam II Criteria
have been modified in order to identify additional individuals who should
undergo genetic testing for HNPCC. These include people with (1) two or more
colon cancers, (2) with colon cancer and a first-degree relative with colon
cancer or another cancer associated with HNPCC before age 50, or an adenomatous
colon polyp before the age of 40, (3) colon or uterine cancer before age 50, and
(4) an adenomatous colon polyp before age 50. The expanded Amsterdam II Criteria
are referred to as the modified Bethesda Criteria.
How is genetic testing done in families suspected of being FAP families?
Almost all mutations that cause FAP occur in one gene, referred to as the APC
gene. If an individual has FAP, that family member should have their APC gene
examined for mutations. If a mutation is found, the same mutation can be sought
in other family members. If a family member has the same mutation, then he or
she will probably develop colon cancer. If that person does not have the
mutation, he or she is not at an increased risk for colon cancer. If there is no
member in the family who clearly has FAP and can undergo genetic testing, then
genetic testing has little value for other family members.
How is genetic testing done in families suspected of being HNPCC families?
Mutations that cause HNPCC occur in several different genes. If an individual
in a family suspected of being in an HNPCC family has colon cancer, tissue from
the cancer can be examined to determine if a mutation is present. If there is a
mutation, then other family members can be examined for the mutation. If they
have the mutation, then they probably will develop colon cancer. If they do not
have the mutation, they are not at increased risk for colon cancer. If there is
no member in the family with colon cancer and an identifiable mutation, then
genetic testing of family members has little value.
Medically reviewed by Jay B. Zatzkin, MD; American Board of Internal Medicine with subspecialty in Medical Oncology
Last Editorial Review: 11/24/2015
"Molecular genetics of colorectal cancer"