Learning About Colon Cancer

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Learning About Colon Cancer

What do we know about heredity and colon cancer?

Colon cancer, a malignant tumor of the large intestine, affects both men and women. In the United States, approximately 160,000 new cases of colorectal cancer are diagnosed each year.

The majority of colon cancer cases are sporadic, which means a genetic mutation may happen in that individual person. However, approximately 5 percent of individuals with colon cancer have a hereditary form, which means that they have inherited a mutation from one of their parents that causes the disease. In those families, the chance of developing colon cancer is significantly higher than in the average person. These hereditary cancers typically occur at an earlier age than sporadic (non-inherited) cases of colon cancer. The risk of inheriting these mutated genes from an affected parent is 50 percent for both males and females.

Scientists have discovered several genes contributing to a susceptibility to two types of colon cancer:

Mutations in MSH2 and MLH1 are the most common mutations that cause HNPCC. A mutation in PMS1 was originally reported in a single family with HNPCC, however, this mutation was not found in all members of the family who had developed the disease. For this reason, the role of PMS1 in HNPCC is currently being questioned.

The genes that cause HNPCC and FAP were relatively easy to discover because they exert strong effects. Other genes that cause susceptibility to colon cancer are harder to discover because the cancers are caused by a number of genes, each of which individually exerts a weak effect.

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Is there a test for hereditary colon cancer?

Gene testing can identify individuals who carry the more common gene mutations associated with FAP or HPNCC, such as those listed above. However, these tests may not identify all gene mutations that cause FAP or HNPCC. In some families, additional mutations may be present that cause the FAP or HNPCC, which cannot be detected by the commonly used gene tests.

The test for FAP syndrome involves examining DNA in blood cells called lymphocytes (white blood cells), looking for mutations in the APC gene. No treatment to reduce cancer risk is currently available for people with APC mutations that are associated with FAP. But for those who test positive, frequent surveillance can detect the cancer at an early, more treatable stage. Because of the early age at which this syndrome appears, the test may be offered to children under the age of 18 if they have a parent known to carry the mutated APC gene.

Researchers hope that an easier test, which is currently experimental, will become available for common use in three to five years. This new test looks for cancer cells with the APC mutation in a stool sample.

Genetic testing for HNPCC involves looking for mutations in four of the five genes identified that are associated with HNPCC - MLH1, MSH2, MSH6, and PMS2.

Individuals in families at high risk of genetic predisposition may consider testing. Genetic counselors can help individuals make decisions regarding testing.

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Current NHGRI Clinical Research on Hereditary Colon Cancer

Currently, NHGRI is not conducting clinical research studies on colon cancer.

  • Current NHGRI Clinical Studies
  • Hereditary Colon Cancer Clinical Trials [clinicaltrials.gov]
  • Clinical Research FAQ
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    Additional Resources for Information on Hereditary Colon Cancer

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    Last Updated: March 22, 2012