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Molecular genetics of colorectal cancer

Harold Frucht, MD
Aimee L Lucas, MD, MS
Section Editors
Richard M Goldberg, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Diane MF Savarese, MD


Colorectal cancer (CRC) is a common disease. Approximately 135,430 new cases are diagnosed each year in the United States, of which 95,520 originate in the colon and the rest in the rectum [1]. Annually, approximately 50,260 Americans die of CRC, accounting for approximately 9 percent of all cancer deaths; in the United States, CRC ranks third in both incidence and cause of cancer death in both men and women. Global, country-specific data on incidence and mortality are available from the World Health Organization (WHO) GLOBOCAN database.

The risk factors for CRC are both environmental and inherited. The mode of presentation of CRC follows one of three patterns that are reflective of these differing risk factors: sporadic, inherited, and familial:

Sporadic disease, in which there is no family history, accounts for approximately 70 percent of all CRCs. It is most common over the age of 50, and dietary and environmental factors have been etiologically implicated. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors".)

Fewer than 10 percent of patients have a true inherited predisposition to CRC, and these cases are subdivided according to whether or not colonic polyps are a major disease manifestation. The diseases with polyposis include familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and the hamartomatous polyposis syndromes (eg, Peutz-Jeghers, juvenile polyposis [2], phosphatase and tensin homolog [PTEN] hamartoma tumor [Cowden] syndrome), while those without polyposis are referred to as hereditary nonpolyposis CRC (HNPCC; Lynch syndrome). These conditions are all associated with a high risk of developing CRC. In many cases, the causative genetic mutation has been identified, and a test is available. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis" and "MUTYH-associated polyposis" and "Peutz-Jeghers syndrome: Epidemiology, clinical manifestations, and diagnosis" and "Juvenile polyposis syndrome" and "PTEN hamartoma tumor syndrome, including Cowden syndrome" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis".)

The third and least well understood pattern is known as "familial" CRC, which accounts for up to 25 percent of cases. Affected patients have a family history of CRC, but the pattern is not consistent with one of the inherited syndromes described above. Individuals from these families are at increased risk of developing CRC, although the risk is not as high as with the inherited syndromes. Having a single affected first-degree relative (ie, parent, child, sibling) increases the risk of developing CRC 1.7-fold over that of the general population. The risk is further increased if two first-degree relatives have CRC or if the index case is diagnosed before age 55. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors".)

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Literature review current through: Nov 2017. | This topic last updated: Mar 23, 2017.
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