Colorectal Cancer

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Causes, Risk Factors, and Prevention TOPICS

Do we know what causes colorectal cancer?

We don't know the exact cause of most colorectal cancers, but a great deal of research is being done 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. But 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 (defects) that turn on oncogenes or turn off tumor suppressor genes. Mutations in several different genes seem to be needed to cause colorectal cancer.

Some DNA mutations may be passed 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 come from the original mutated cell. These DNA changes are due to 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 their effects on the growth of cells are now known.

For example, inherited changes in a gene called APC 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, causing hundreds of polyps to form 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 non-polyposis colon cancer (HNPCC), also known 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. A mutation in one of the DNA repair enzyme genes like MLH1, MSH2, MLH3, MSH6, PMS1, or PMS, may allow DNA errors to go uncorrected. These errors will sometimes affect growth-regulating genes, which may lead to the development of cancer. TGFBR2 is another gene linked to HNPCC. It helps regulate cell growth.

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 can detect gene mutations associated with these inherited syndromes. If you have a family history of colorectal polyps or cancer or other symptoms linked to these syndromes, you may want to ask your doctor about genetic counseling and genetic testing. The American Cancer Society recommends discussing genetic testing with a qualified cancer genetics professional before any genetic testing is done. For more on this, see our document Genetic Testing: What You Need to Know.

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. There are certain risk factors that probably play a role in causing these acquired mutations, but so far it's not known what causes most of them.

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 KRAS, TP53, and SMAD4. These changes can lead the cells to grow and spread uncontrollably. Other genes that aren't known yet are likely involved as well.

For more information about how genes changes can lead to cancer, see our document Genes and Cancer.

Last Medical Review: 10/15/2014
Last Revised: 08/13/2015