Do We Know What Causes Colorectal Cancer?

Researchers have found several factors that can increase a person’s risk of colorectal cancer, but it’s not yet clear exactly how all of these factors might cause this cancer.

Cancer is caused by changes in the DNA inside our cells. DNA is the chemical in our cells that makes up our genes, which control how our cells function. DNA, which comes from both our parents, affects more than just how we look.

Some genes help control when our cells grow, divide into new cells, and die:

  • Certain genes that help cells grow, divide, and stay alive are called oncogenes.
  • Genes that help keep cell division under control 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, resulting in cells growing out of control. Changes in many different genes are usually needed to cause colorectal cancer.

Inherited gene mutations

Some DNA mutations can be passed from generation to generation and are found in all cells in the body. When this happens, we say the mutations are inherited. A small portion of colorectal cancers are caused by inherited gene mutations. Many of these DNA changes and their effects on the growth of cells are now known. For example:

  • Familial adenomatous polyposis (FAP) and Gardner syndrome are caused by inherited changes in the APC gene. The APC gene is a tumor suppressor gene; it normally helps keep cell growth in check. In people with 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 more gene mutations will happen in the cells of the polyps.
  • Lynch syndrome (hereditary non-polyposis colon cancer, or HNPCC) is caused by changes in genes that normally help a cell repair damaged DNA. A mutation in one of the DNA repair enzyme genes like MLH1, MSH2, MLH3, MSH6, PMS1, and PMS2, can allow DNA errors to go unfixed. These errors will sometimes affect growth-regulating genes, which may lead to the development of cancer. 
  • Peutz-Jeghers syndrome is caused by inherited changes in the STK11 (LKB1) gene, a tumor suppressor gene.
  • MUTYH-associated polyposis is caused by mutations in the MUTYH gene, which is involved in how the cell “proofreads” or checks the accuracy of DNA when cells divide. 

Special 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  Understanding Genetic Testing for Cancer and What Happens during Genetic Testing for Cancer?

Acquired gene mutations

Some gene 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.

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. Certain risk factors probably play a role in causing these acquired mutations, but so far it’s not known what causes most of them.

There doesn’t seem to be a single genetic 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 probably involved as well.

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

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Libutti SK, Salz LB, Willett CG, Levine RA. Chapter 57: Cancer of the colon. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

Van Schaeybroeck S, Lawler M, Johnston B, et al. Ch. 77 Colorectal cancer. In: Neiderhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier; 2014.

 

 

Last Medical Review: October 15, 2016 Last Revised: April 14, 2017

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