The Genetics of Colorectal Cancer

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The summary below is from the full report titled "The Genetics of Colorectal Cancer." It is in the 1 October 2002 issue of Annals of Internal Medicine (volume 137, pages 603-612). The authors are PM Calvert and H Frucht.

What is the problem and what is known about it so far?

Colorectal cancer, which affects the colon [large intestine] or rectum, is a common type of cancer. Most cases occur in people with no special genetic susceptibility to colorectal cancer. However, some cases of colorectal cancer occur in people whose genes put them at high risk. Their colorectal cancer can be either inherited or familial. Colorectal cancer is inherited in fewer than 10 out of every 100 cases. People with inherited colorectal cancer have polyposis or nonpolyposis syndromes. In polyposis syndromes, patients develop many polyps in their colons. Some of these polyps become cancer. Some patients do not have polyposis but do have inherited genes that put them at very high risk for colorectal cancer. Colorectal cancer is familial in possibly up to 25 of every 100 cases. People in families with familial colorectal cancer have a higher than average risk for colorectal cancer, but the pattern of inheritance is not consistent with an inherited colorectal cancer syndrome. Screening prevents colorectal cancer deaths by 1) finding and removing noncancerous outgrowths of the colon or rectum [polyps] before they become cancer and 2) finding cancer at early, curable stages. Knowing if someone had a risk for inherited or familial colorectal cancer would help to plan the intensity of screening.

Why did the authors do this review?

To summarize what is known about the kinds of gene abnormalities (mutations) that cause colorectal cancer.

How did the authors do this review?

The authors reviewed the literature on the types of gene mutations related to colorectal cancer. They focused on how doctors should identify, advise, and test patients who are at risk for inherited or familial colorectal cancer.

What did the authors find?

Four major types of gene mutations can lead to colorectal cancer. First, mutations in oncogenes, which help to control cell division, can lead to uncontrolled cell division and tumor formation. Second, mutations in the tumor suppressor genes that counteract uncontrolled cell division, which can result in cancer, cause them to lose this important function. People with polyposis have inherited a mutated tumor suppressor gene called the APC gene. Third, mutations in mismatch repair genes, which act to repair mistakes that occur in the formation of the genetic material, DNA, result in mistakes that can lead to cancer. People with the Lynch syndrome have inherited an abnormal mismatch repair gene. Fourth, more subtle gene changes, known as polymorphisms, are found in people with familial colorectal cancer.

What are the implications of the review?

Doctors should consider genetic testing when a patient has polyposis; a relative who had colorectal cancer before 45 years of age; or more than one first-degree relative (parent, sibling, or child) with colorectal cancer, uterine cancer, or ovarian cancer. Testing has some serious consequences: It is expensive, and the results are sometimes misleading. People with a cancer susceptibility gene can have difficulty obtaining insurance. A genetic counselor should be involved before genetic tests for colorectal cancer are performed and should be available afterward to discuss the results with patients.