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Colon Cancer
  Considering Genetic Testing

By Miriam Komaromy, MD

Reviewed by Peggy Conrad, MS, CGC and Jonathan Terdiman, MD





In order to diagnose the two most common hereditary colon cancer syndromes — hereditary nonpolyposis colorectal cancer (HNPCC), and familial adenomatous polyposis (FAP) — doctors mainly depend on the results of your physical exam and information about your family medical history. In general, they do not rely on genetic testing to make an initial diagnosis. However, under some circumstances genetic testing is also an appropriate tool for diagnosis. (For recent news about genetic testing in people at risk for colon cancer, see Related News below.)

 
 
 

When Is Testing Appropriate?

If you are uncertain about your level of risk for inherited colon cancer, you should use Genetic Health's TreeBuilder tool which will help you assess the risk in your family.
Genetic testing for colon cancer is often appropriate if you have a family medical history that's strongly suggestive of familial or hereditary colon cancer. The results of a genetic test can indicate which family members have inherited a mutated gene and thus an increased risk of cancer. This is important information, since it will affect your screening and prevention options, and indicate whether your children or siblings are at risk.

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Who Should Get A Genetic Test?

If your family medical history shows that you are at increased risk for hereditary colon cancer, you may want to talk to your doctor or genetic counselor about genetic testing for a specific colon cancer-related mutation. If you are a healthy person with a strong family history of cancer, you may be surprised to find that your health care provider does not want to perform a genetic test on you. Instead, he or she will recommend that one of your family members who actually has cancer or multiple polyps be tested. This person is often referred to as an affected family member. If an affected family member tests positive for a known mutation, then other people in the family can be tested for that same mutation. If no mutation can be found in an affected person, it means that the mutation responsible for that family's high incidence of colon cancer has not yet been discovered and it would be pointless for other family members to undergo genetic testing.

The likelihood that an affected family member will have a mutation is much higher than it is for an unaffected family member. However, if no affected family members are available (or willing) to take a genetic test, sometimes a doctor or genetic counselor will agree to test an unaffected family member. If a mutation is found in an unaffected family member, then you have useful medical information. Unfortunately, if no mutation is found, this doesn't definitively rule out the possibility that this individual has inherited a genetic syndrome. The unaffected person may have not inherited a mutation that causes colon cancer syndromes, but they also could still have inherited a mutation that has not yet been discovered and thus does not show up in genetic tests.

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Getting a Genetic Test

A medical geneticist or genetic counselor can order a genetic test as part of a consultation. In addition, your regular doctor can also order such a test if he or she considers it appropriate. Whichever route you take, it's important that you obtain your genetic test through a health care provider who is knowledgeable about inherited colon cancer. In this way, you ensure that you get the correct genetic test and that the results — as well as the issues involved — are clearly explained.

The genetic test itself is a simple process that usually involves drawing a small amount of blood from your arm for analysis by a testing lab. (The test is usually performed on DNA taken from white blood cells.) The analysis, however, can take weeks or even months to complete because the DNA must first be isolated and then time-consuming genetic tests performed. Then the tests have to be repeated to confirm any positive result. Both the time it takes to receive your results and the cost of testing will vary, depending on the type of test being performed and the particular lab running the test.

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Genetic Tests Are Often Misinterpreted by Doctors From A Wide Variety of Specialties


A 1997 study looked at use of genetic testing for FAP and found that:

  • Less than 20 percent of patients received genetic counseling or signed written informed consent before undergoing genetic testing.
  • Doctors misinterpreted test results in more than 30 percent of cases, providing patients with false assurance that they did not have FAP when in fact their results were inconclusive.

Patients undergoing genetic testing need to be well informed about the tests and need to find health care providers with training and experience in genetic testing and test interpretation.


After Testing, What Next?

Once a harmful mutation has been identified in a family, other family members can be tested for the same mutation. This type of subsequent testing is usually faster and less expensive than the initial test because the lab will be looking for one particular mutation rather than all possible mutations in colon cancer-related genes. Such tests are also highly accurate and reliable. By undergoing this type of testing, families can sort out who has and who hasn't inherited the mutation. Those family members who have the mutation will need to undergo more intensive screening and prevention efforts. Those who are free of the mutation will be able to follow the simpler cancer screening and prevention recommendations for the general public.

If no mutation is found in an affected family member, there's usually no reason to test other family members. In effect, the genetic cause of this particular family's cancer syndrome has not been determined. However, because the disease evidently "runs in the family" — even though the cause has not be identified — all family members should act as though they are at high risk for cancer and follow the screening guidelines recommended for people with inherited genetic risk for cancer.
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Informed Consent

Always remember, you have a right to be fully informed about the risks, benefits, and limitations of any test you are considering before you take it. Among other things, you need to understand why this test is appropriate for you, how your test results can predict your risk of cancer or other illness, and how these results will impact your screening and prevention options. You also need to understand your chances of getting an uninformative test result, as well as the anxiety or distress that can be caused by such tests. Finally, you must be aware of the possible loss of confidentiality and discrimination that can result from such tests.

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More on Informed Consent (Coming Soon)

A Genetic Testing Case Study

To better understand the specifics of genetic testing, let's consider the case of 35-year-old Mary, whose mother died of colon cancer at age 50. She also had a cousin who died of colon cancer at age 45, and an uncle diagnosed with the disease a year ago at age 52 who is currently undergoing treatment.

Under some circumstances, Mary's doctor might test her for alterations in the genes associated with HNPCC. However, if the results are negative — no mutations are found — the test result yields more questions than answers. Because no mutation has been identified as the culprit for the cancers in Mary's family, no one can be certain whether there is a detectable mutation in the family that Mary simply did not inherit, or whether there is no detectable mutation in the family at all. The doctor can't do much to reassure Mary because he has no information to explain the clustering of her family's early-onset colon cancer. Something is causing it, although it is not necessarily a mutation of this particular gene. Thus Mary may still be at increased risk for the disease, just not for this reason.

If, on the other hand, Mary's doctor had recommended that testing begin with her uncle (who has cancer and is thus an affected family member), the interpretation of the test results would be quite different. If tests showed that Mary's uncle had a mutation known to cause HNPCC, Mary could be tested for the same mutation — a much less expensive process than being tested for all known mutations. If Mary's test results indicated that she did not have the same mutation as her uncle, she could feel greatly reassured: her uncle's test results reveal the cause of the cancer cluster in her family — an identifiable mutation — and Mary did not inherit it. This means that Mary is no more likely to develop colon cancer than members of the general population, despite her worrisome family history.
 

 

 


Related News
In order to view these articles you will need to have a MyGeneticHealth account. If you are not already a member, selecting the article will automatically take you to a page where you can sign up.
Many at risk of colorectal cancer have reservations about genetic testing

References

Petersen, G. et al. (1999). Genetic testing and counseling for hereditary forms of colorectal cancer. Cancer 86: 1720-30.

Giardello, F. et al. (1997). The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N Engl J Med 336: 823-7.

Geller, G. et al. (1997). Genetic testing for susceptibility to adult-onset cancer: the process and content of informed consent. JAMA 277:1467-1474.

Terdiman, J. et al. (1999). Genetic testing in hereditary colorectal cancer: Indications and procedures. The American Journal of Gastroenterology 94(9): 2344-2356.

 

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