Although we do not know the exact cause of most colorectal cancers, there is a great deal of research in this area.

Researchers are beginning to understand how certain changes in DNA can cause normal cells to become cancerous. DNA is the chemical in each of our cells that makes up our genes -- the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than just how we look.

Some genes contain instructions for controlling when our cells grow, divide, and die. Certain genes that speed up cell division or help cells to live longer are called oncogenes. Others that slow down cell division, or cause cells to die at the right time, are called tumor suppressor genes. Cancers can be caused by DNA mutations (changes) that "turn on" oncogenes or "turn off" tumor suppressor genes. Changes in several different genes seem to be needed to cause colorectal cancer.

Some DNA mutations may be passed on from generation to generation and are found in all cells in the body. When this happens, we say the mutations are inherited. Other mutations happen during a person's lifetime and are not passed on. They affect only cells that originate from the cell that first mutated. These DNA changes are called acquired mutations. These are the most common type of mutations. Some of the same genes are involved in both hereditary and acquired mutations.

Inherited gene mutations

A small portion of colorectal cancers are known to be caused by inherited gene mutations. Many of these DNA changes and how they can change the growth control of cells are now known.

Inherited changes in a gene called APC, for example, are responsible for familial adenomatous polyposis (FAP) and Gardner syndrome. The APC gene is a tumor suppressor gene -- it normally helps keep cell growth in check. In people who have inherited changes in the APC gene, this "brake" on cell growth is turned off, resulting in the formation of hundreds of polyps in the colon. Over time, cancer will nearly always develop in one or more of these polyps because new gene mutations occur in the cells of the polyps.

Hereditary nonpolyposis colon cancer (HNPCC), also know as Lynch syndrome, is caused by changes in genes that normally help a cell repair faulty DNA. Cells must make a new copy of their DNA each time they divide into 2 new cells. Sometimes errors are made when copying the DNA code. Fortunately, cells have DNA repair enzymes that act like proofreaders or spell checkers. Mutations in DNA repair enzyme genes such as MLH1, MSH2, MSH6, or PMS2 may allow DNA errors to go uncorrected. These errors will sometimes affect growth-regulating genes, which may lead to the development of cancer.

The rare Peutz-Jeghers syndrome is caused by inherited changes in the STK11 gene. This seems to be a tumor suppressor gene, although its exact function is not clear.

Genetic tests are available that can detect gene mutations associated with these inherited syndromes. As mentioned in "What are the risk factors for colorectal cancer?" people with a family history of colorectal polyps or cancer or other symptoms linked to these syndromes may want to ask their doctor about genetic counseling and genetic testing. The American Cancer Society recommends discussing genetic testing with a qualified genetic counselor before genetic testing is done.

Acquired gene mutations

In most cases of colorectal cancer, the DNA mutations that lead to cancer are acquired during a person's life rather than having been inherited. While certain risk factors likely play a role in causing these acquired mutations, so far the cause of most of these mutations remains unknown.

There does not seem to be a single pathway to colorectal cancer that is the same in all cases. In many cases, the first mutation occurs in the APC gene. This leads to an increased growth of colorectal cells because of the loss of this "brake" on cell growth. Further mutations may then occur in genes such as K-ras, p53, and SMAD4. These changes can lead the cells to grow and spread uncontrollably. Other, as of yet unknown, genes are likely involved as well.

Last Medical Review: 05/18/2009
Last Revised: 05/18/2009