All cancers involve changes in genes. These changes are called mutations.
Most cases of colorectal cancer are due to mutations that happen randomly.
However, in some families the genetic changes may be inherited and passed on
from one generation to the next. These cancers are referred to as hereditary
How often is colorectal cancer inherited?
Though most cases occur randomly, it is estimated that 5 to 10 percent of
colorectal cancer cases are hereditary in nature.1
How can I find out if there is a chance that the colorectal cancer
in my family is hereditary?
By taking a detailed family health history and personal medical history,
your doctor can advise you whether your personal and family health history
suggest hereditary colorectal cancer. Risk factors include:
- A personal or family history of colorectal cancer diagnosed before the age
- A personal or family history of multiple colon polyps
- Multiple family members with colorectal cancer, especially close blood
relatives (parents, children, brothers, sisters, grandparents, aunts, or
In such cases, genetic counseling and genetic testing may be recommended.
Genetic testing looks for changes in your genes that indicate you have, or you
may develop, a hereditary form of colorectal cancer. A genetic counselor
can explain the
risks and benefits of genetic testing.
What specific types of colorectal cancer are inherited?
Two relatively rare hereditary conditions that involve a very high lifetime
risk for colorectal cancer are Lynch syndrome, also known as hereditary
nonpolyposis colorectal cancer, and familial adenomatous polyposis (FAP). There
are other colorectal cancer syndromes that are known to be hereditary, in
addition to these two. Some are related to the occurrence of multiple polyps,
whereas others are associated with conditions such as brain cancer and certain
types of skin cancer.
What is Lynch syndrome or hereditary nonpolyposis colorectal cancer
Lynch syndrome is a rare inherited condition that carries a high risk of
developing colorectal cancer. Lynch syndrome is also known as hereditary
nonpolyposis colorectal cancer (HNPCC). An estimated three out of every 100
colorectal cancers are thought to be caused by Lynch syndrome. 2 For
people with Lynch syndrome, the lifetime risk of developing colorectal cancer by
age 70 is about 45% for men and 35% for women. 3
Families that have Lynch syndrome usually have more cases of colorectal
cancer than would be expected in the general population. The syndrome is
also associated with an increased risk for cancers of the uterus, ovary,
stomach, small intestine, liver, bile duct, urinary tract, and the brain and
central nervous system. Lynch syndrome also causes colorectal cancer to
occur at an earlier age than it might in the general population. The average age
for a person with Lynch syndrome to be diagnosed with colorectal cancer is 44 as
compared with the average age of 72 for a new diagnosis of colorectal cancer in
the general population. 4
The syndrome is caused by mutations in specific genes, the most frequent of
which are MLH1, MSH2, MSH6, and PMS2 . Research is
also ongoing to identify other genes associated with Lynch syndrome.
If you have a family history that suggests Lynch syndrome, you may want to
consider a more extensive evaluation by a doctor and counseling by a genetic
counselor. Based on your individual situation, this may help you to develop
an appropriate strategy for dealing with your cancer risk, which could include
If you have been newly diagnosed with colorectal cancer, you may also want
to consider genetic testing for Lynch syndrome to determine if you have an
associated genetic mutation. If you test positive for a Lynch syndrome
genetic mutation, then you could make your blood relatives aware that they may
also be at an increased risk for developing colorectal cancer and that they may
want to receive genetic counseling and genetic testing to determine appropriate
medical management for themselves. There is sufficient evidence to suggest that
such a strategy can improve clinical outcomes for relatives with Lynch syndrome.
What is familial adenomatous polyposis (FAP)?
FAP is another rare form of hereditary colorectal cancer. FAP accounts
for less than 1% of colorectal cancers. 5 People with FAP
often develop hundreds to thousands of polyps (i.e., growths in the colon or
rectum) that are initially not cancerous, but which eventually develop into
cancer if not treated. More than 95% of people with FAP develop polyps by
age 35, with the average age being in the mid-teens. 6 If
FAP is not recognized and treated, there is almost a 100% chance that a
person will develop colorectal cancer. There is also an increased chance of
polyps and cancer to develop in the stomach and/or small intestine.
FAP is caused by a mutation on the APC gene, which is known to
be a tumor suppressor gene. Mutations result in a loss of the ability to
restrict tumor growth, thereby giving rise to cancer.
FAP is typically diagnosed by symptoms and the presence of more than 100
adenomatous colon polyps. People with FAP can also have a genetic test to
look for a mutation in the APC gene. If you have a family history of
FAP, it is important to discuss with your doctor your screening options.
What are the benefits of genetic testing for colorectal cancer?
- Genetic test results may allow for a more accurate assessment of a
person’s cancer risk. If the results are positive, health care providers can
screen at an earlier age to look for colorectal cancer and other possible
cancers. If the results are negative, individuals may not have to be
screened as aggressively.
- If a mutation is identified, genetic testing and/or early cancer screening
can be offered to other family members who may be at an increased risk.
What are the risks of genetic testing for colorectal cancer?
- Genetic testing can be emotionally difficult regardless of the results.
- If a mutation is found, relatives who have not had genetic testing may
make false assumptions about their own genetic status.
- The costs associated with cancer screening and prevention for people with
mutations may or may not be covered by their health insurance provider.
- Results could be used by an employer or insurance company to discriminate
against an individual. However, national legislation, known as the Genetic
Information Nondiscrimination Act of 2008 , has been passed to protect
against the improper use of genetic information in health insurance and
What information should be provided to me before I receive genetic
Your doctor should give you information about genetic testing in order for
you to decide whether or not you wish to undergo such testing. The American
Society of Clinical Oncology has developed a list of items that should be
included in a comprehensive document to be used for informed consent. 7
- Information on the specific test being performed
- Implications of positive and negative results
- Possibility that the test will not be informative
- Options for risk estimation without genetic testing
- Risk of passing a mutation to children
- Technical accuracy of the test
- Fees involved in testing and counseling
- Risks of psychologic distress
- Risks of insurer or employment discrimination
- Confidentiality issues
- Options and limitations of medical surveillance and screening following
Where can I get more information?
A person who is considering genetic testing should speak with a
professional trained in genetics before deciding whether to be tested. A genetic
counselor can discuss the benefits and risks of genetic testing and can explain
what genetic testing can and can’t tell you. For more information on
genetic testing or for help finding a health care professional trained in
genetics, refer to the resources and links listed below.
INFORMATION ABOUT GENETIC TESTING
Family Cancer Syndromes , American Cancer Society
General Public: Genetic Testing for Lynch Syndrome ,
Centers for Disease Control and Prevention
Help Me Understand Genetics: Genetic Testing , U.S.
National Library of Medicine
Cancer Genetics Services Directory of the National Cancer
A directory of individuals who provide services related to
cancer genetics (cancer risk assessment, genetic counseling, genetic
susceptibility testing, and others). http://www.cancer.gov/search/geneticsservices/
Genetics of Colorectal Cancer - Health Professional Version
, National Cancer Institute
Major Genetic Syndromes
Colorectal Cancer , Cancer.Net
What is familial adenomatous polyposis?
What is Lynch Syndrome?
Genetics & Family History , Colon Cancer Alliance
1 Lynch HT, De la Chapell A. Hereditary colorectal cancer. N Engl J
Hampel H, Frankel WL, Martin E, et al. Screening for the
Lynch syndrome (hereditary
nonpolyposis colorectal cancer).
N Engl J Med 2005;352:1851-1860.
McClain MR, Melillo S, et al. EGAPP supplementary evidence review: DNA
strategies aimed at reducing morbidity and mortality from Lynch syndrome.
Kohlmann W, Gruber SB (Updated November 29, 2006). Hereditary
Colon Cancer. In: GeneReviews at
GeneTests: Medical Genetics Information Resource
(database online). Copyright,
University of Washington, Seattle. 1993-2009. Available at
. Accessed February 19, 2009.
5 Evaluation of Genomics Applications in
Practice and Prevention Working Group.
Recommendations from the EGAPP
Working Group: genetic testing strategies in newly
diagnosed individuals with
colorectal cancer aimed at reducing morbidity and mortality
from Lynch syndrome in
relatives. Genet Med 2009:11(1):35-41.
6 American Society of
Clinical Oncology. Cancer. Net Guide to Familial Adenomatous
Polyposis. Available at
February 5, 2009.
ASCO Subcommittee on Genetic Testing for Cancer Susceptibility. Statement
American Society of
Clinical Oncology. Genetic testing for cancer susceptibility.
J Clin Oncol