Cancer Health Center
Genetics of Colorectal Cancer - Introduction
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Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.
Colorectal cancer is the third most commonly diagnosed cancer in both men and women. In 2009, an estimated 146,970 new cases will be diagnosed, and 49,920 deaths from colorectal cancer will occur.[1] Two kinds of observations indicate a genetic contribution to colorectal cancer risk: (1) increased incidence of colorectal cancer among persons with a family history of colorectal cancer; and (2) families in which multiple family members are affected with colorectal cancer, in a pattern indicating autosomal dominant inheritance of cancer susceptibility.[2,3,4,5,6] About 75% of patients with colorectal cancer have sporadic disease, with no apparent evidence of having inherited the disorder. The remaining 25% of patients have a family history of colorectal cancer that suggests a genetic contribution, common exposures among family members, or a combination of both. Genetic mutations have been identified as the cause of inherited cancer risk in some colon cancer-prone families; these mutations are estimated to account for only 5% to 6% of colorectal cancer cases overall. It is likely that other undiscovered major genes and background genetic factors contribute to the development of colorectal cancer, in conjunction with nongenetic risk factors.
Natural History of Colorectal Cancer
Colorectal tumors present with a broad spectrum of neoplasms, ranging from benign growths to invasive cancer, and are predominantly epithelial-derived tumors (i.e., adenomas or adenocarcinomas). Pathologists have classified the lesions into three groups: nonneoplastic polyps, neoplastic polyps (adenomatous polyps, adenomas), and cancers. While most adenomas are polypoid, flat and depressed lesions may be more prevalent than previously recognized. Large flat and depressed lesions may be more likely to be severely dysplastic, although this remains to be clearly proven.[7,8] Specialized techniques may be needed to identify, biopsy, and remove such lesions.[9] The nonneoplastic polyps include hyperplastic, juvenile, hamartomatous, inflammatory, and lymphoid polyps, which have not generally been thought of as precursors of cancer. Research, however, suggests increased colorectal cancer risk in some families with multiple members affected with juvenile polyposis and hyperplastic polyposis.[10,11,12]
Epidemiologic studies have shown that a personal history of colon adenomas places one at an increased risk of developing colon cancer.[13] Two complementary interpretations of this observation are (1) the adenoma may reflect an innate or acquired tendency of the colon to form tumors, and (2) adenomas are the primary precursor lesion of colon cancer. More than 95% of colorectal cancers are carcinomas, and about 95% of these are adenocarcinomas. It is well recognized that adenomatous polyps are benign tumors that may undergo malignant transformation. They have been classified into three histologic types, with increasing malignant potential: tubular, tubulovillous, and villous. While there is no direct proof that most colorectal cancers arise from adenomas, adenocarcinomas are generally considered to arise from adenomas,[14,15,16,17,18] based upon these important observations: (1) benign and malignant tissue occur within colorectal tumors;[19] and (2) when patients with adenomas were followed for 20 years, the risk of cancer at the site of the adenoma was 25%, a rate much higher than that expected in the normal population.[20] Also, three characteristics of adenomas that are highly correlated with the potential to transform into cancer include large size, villous pathology, and the degree of dysplasia within the adenoma.[19] In addition, removal of adenomatous polyps is associated with reduced colorectal cancer incidence.[21,22]
WebMD Public Information from the National Cancer Institute
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Genetics of Colorectal Cancer Topics
Microscopic particles called “nanoshells” are injected into cancer patients’ bloodstream to help doctors track and destroy tumors.
