DPH: Genetic Evaluation and Testing for Hereditary Colorectal Cancer: What You Should Know
Colorectal Cancer

Genetic Evaluation and Testing for Hereditary Colorectal Cancer: What You Should Know

 
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 cancers.
 
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 of 50
  • 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 uncles)
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 (HNPCC)?
 
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 genetic testing.
 
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. 5
 
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 employment.
What information should be provided to me before I receive genetic testing?
 
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 Items include:
  1. Information on the specific test being performed
  2. Implications of positive and negative results
  3. Possibility that the test will not be informative
  4. Options for risk estimation without genetic testing
  5. Risk of passing a mutation to children
  6. Technical accuracy of the test
  7. Fees involved in testing and counseling
  8. Risks of psychologic distress
  9. Risks of insurer or employment discrimination
  10. Confidentiality issues
  11. Options and limitations of medical surveillance and screening following testing.
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 Institute. 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/
 
Find a Genetic Counselor Near You - Resource Link , National Society of Genetic Counselors
http://www.nsgc.org/p/cm/ld/fid=164
 
Genetics of Colorectal Cancer - Health Professional Version , National Cancer Institute
Major Genetic Syndromes
 
Colorectal Cancer , Cancer.Net
Colorectal Cancer

What is familial adenomatous polyposis?

What is Lynch Syndrome?

Genetics & Family History , Colon Cancer Alliance
 
 
References
 
   Lynch HT, De la Chapell A. Hereditary colorectal cancer. N Engl J Med 2003;348:919-932.
    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.
    Palomaki GE, McClain MR, Melillo S, et al. EGAPP supplementary evidence review: DNA
      testing strategies aimed at reducing morbidity and mortality from Lynch syndrome.
      Genet Med 2009;11:42-65.
    Kohlmann W, Gruber SB (Updated November 29, 2006). Hereditary Non-Polyposis
      Colon Cancer. In: GeneReviews at GeneTests: Medical Genetics Information Resource
      (database online). Copyright, University of Washington, Seattle. 1993-2009. Available at
      http://www.genetests.org . Accessed February 19, 2009.
   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
      Accessed on February 5, 2009.
7       ASCO Subcommittee on Genetic Testing for Cancer Susceptibility. Statement of the
      American Society of Clinical Oncology.  Genetic testing for cancer susceptibility.
      J Clin Oncol 1996;14:1730-1736.




Content Last Modified on 7/21/2016 11:42:08 AM