Colon Cancer, The Genetic Factor

Medical Author: Dennis Lee, MD
Medical Editor: Jay W. Marks, MD, and Barbara K. Hecht, Ph.D.


Colon cancer is the fourth most common cancer in the United States. In the US an estimated 130,000 men and women will develop colon cancer and more than 50,000 will die from it each year. The life-time risk for individuals to develop colon cancer is approximately 6%, but the risk increases to 18% among individuals who have a first degree relative (parent, sibling or child) with colon cancer.

What causes colon cancer?

Mutant genes cause colon cancer. The human body is composed of trillions of cells. Inside each cell are two sets of 23 chromosomes, one set from each parent. Each chromosome contains long strands of DNA. The DNA encodes thousands of genes. The genes carry the genetic information that is passed down from both parents. Different genes are responsible for different structures and functions in the body. For example, some genes influence eye color, hair color, height, and other physical characteristics. Other genes regulate cell growth and division. Still other genes prevent cells from invading neighboring tissues or spreading to distant organs.

When genes that normally control cell multiplication and growth mutate (change), the cells may multiply and grow without restraint. When cells grow without restraint inside the colon, a colon polyp develops. If additional genetic changes occur in that polyp, the polyp can turn cancerous and invade adjacent tissue and spread to distant sites. The sequence of events by which polyps form, become cancerous, invade nearby tissue and spread can and often does take years.

How does one acquire the mutations that cause colon cancer?

Mutations (changes within individual genes) can be inherited from either or both parents or can be acquired any time after conception. Environmental factors such as radiation, chemicals, oxidants, and viruses may trigger these types of mutations.

Inherited mutations will end up in every cell in the body, whereas acquired mutations will be present only in the original cell in which it occurred and in all the cells descended from that original cell. For example, the mutation may be restricted to the cells of the polyp or cancer.

Generally, acquired mutations tend to cause only one or a few colon polyps that can be removed by colonoscopy. (For further information, please see the article on colonoscopy.) Removing these polyps effectively prevents the progression from colon polyp to colon cancer.

On the other hand, inherited gene mutations present in every cell have a tendency to cause numerous (sometimes thousands) of colon polyps. These polyps may be too numerous or too large to be removed by colonoscopy. In addition, the progression from polyp to invasive cancer may be so rapid that even frequent colonoscopy is not adequate to remove the polyps and prevent colon cancer.

Finally, some cancers may develop directly from cells of the colon lining, without the development of polyps that can be recognized and removed. For this reason, surgical removal of the colon may be necessary to prevent colon cancer in patients with inherited forms of colon cancer.

What are hereditary colon cancer syndromes?

Hereditary colon cancer syndromes are caused by specific inherited mutations that are sufficient in themselves to cause colon polyps, colon cancers, and non-colonic cancers. Hereditary colon cancer syndrome can affect multiple members of a family. Approximately 5% of all colon cancers in the US are due to hereditary colon cancer syndromes. Patients who have inherited one of these syndromes have an extremely high risk for developing colon cancer, approaching 90%-100%. Fortunately, blood tests are now available to test for these hereditary colon cancer syndromes, once a syndrome has been suspected within a family.

Familial adenomatous polyposis (FAP)

Familial adenomatous polyposis, or FAP is a hereditary colon cancer syndrome in which the affected family members develop large numbers (hundreds, sometimes thousands) of colon polyps starting in their teens. Unless the condition is detected and treated early (treatment involves removal of the colon), a family member with the FAP syndrome is almost sure to develop colon cancer. Cancers most commonly begin to appear when patients are in their 40's, but can appear earlier. These patients also are at risk of developing other cancers such as cancers of the thyroid gland, stomach, and the ampulla (the part of the duodenum into which the bile ducts drain).