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Learning About Hereditary 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 year 2000, there were an estimated 130,200 cases diagnosed. The vast majority of colon cancer cases are not hereditary. However, approximately 5 percent of individuals with colon cancer have a hereditary form. In those families, the chances of developing colon cancer is significantly higher than in the average person.

Scientists have discovered several genes contributing to a susceptibility to two types of colon cancer: FAP (familial adenomatous polyposis) and HNPCC (hereditary nonpolyposis colorectal cancer). The risk of inheriting these mutated genes from an affected parent is 50 percent for both males and females. These hereditary cancers typically occur at an earlier age than sporadic (non-inherited) cases of colon cancer.

FAP (familial adenomatous polyposis)
So far, only one FAP gene has been discovered - the APC gene on chromosome 5. But over 300 different mutations of that gene have been identified. Individuals with this syndrome develop many polyps in their colon. People who inherit mutations in this gene have a nearly 100 percent chance of developing colon cancer by age 40.

HNPCC (hereditary non-polyposis colorectal cancer)
Individuals with an HNPCC gene mutation have an estimated 80 percent lifetime risk of developing colon or rectal cancer. However, these cancers account for only three to five percent of all colorectal cancers.

So far, four HNPCC genes have been discovered:

1.hMSH2 on chromosome 2, which accounts for 60 percent of HNPCC colon cancer cases.
2.hMLH1 on chromosome 3, which accounts for 30 percent of HNPCC colon cancer cases.
3.hPMSI on chromosome 2, which accounts for 5 percent of HNPCC colon cancer cases.
4.hPMS2 on chromosome 7, which accounts for 5 percent of HNPCC colon cancer cases.

Together, FAP and HNPCC gene mutations account for approximately 5 percent of all colorectal cancers. The genes that cause these two syndromes 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 interplay among a number of genes, which individually exert a weak effect.

Is there a test for hereditary colon cancer?

Gene testing can identify some individuals who carry genes for FAP and some HPNCC cases of colon cancer. However, the tests are not perfect at this point in time. So, some families may have alterations in the FAP or HNPCC gene that can not be detected.

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 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 people under 18 who have a parent known to carry the mutated gene.

Researchers hope that an easier test, now experimental, will become available in three to five years. This new test examines a stool sample and looks for cancer cells sloughed off by the APC gene.

Genetic tests for HNPCC are of limited value since the current test can identify only a few mutations on two genes that cause HNPCC (hMSH2 and hMLH1). There are no clinical tests for the other two HNPCC genes.

Because of the limitations of available tests for hereditary colon cancer, testing is not recommended for the general population. However, individuals in families at high risk may consider testing. Genetic counselors can help individuals make decisions regarding testing.

Source: National Human Genome Research Institute at www.genome.gov.
February 2003