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Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Introduction

Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.

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 (CRC) is the third most commonly diagnosed cancer in both men and women.

Estimated new cases and deaths from CRC in 2013:[1]

  • New cases: 142,820.
  • Deaths: 50,830.

The following two kinds of observations indicate a hereditary contribution to CRC risk:[2,3,4,5,6]

  1. Increased incidence of CRC among persons with a family history of CRC.
  2. Early onset of CRC, which is suggestive, but not always indicative, of heritability.

About 75% of patients with CRC have sporadic disease with no apparent evidence of having inherited the disorder. The remaining 25% of patients have a family history of CRC that suggests a hereditary 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 CRC cases overall. It is likely that other undiscovered genes and background genetic factors contribute to the development of familial CRC in conjunction with nongenetic risk factors.

(Refer to the PDQ summaries on Colorectal Cancer Screening; Colorectal Cancer Prevention; Colon Cancer Treatment; and Rectal Cancer Treatment for more information about sporadic CRC.)

Natural History of CRC

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 the following three groups:

  1. Nonneoplastic polyps (hyperplastic, juvenile, hamartomatous, inflammatory, and lymphoid polyps), which have not generally been thought of as precursors of cancer.
  2. Neoplastic polyps (adenomatous polyps, and adenomas).
  3. Cancers.

Research, however, suggests increased CRC risk in some families who have multiple members affected with juvenile polyposis, Peutz-Jeghers syndrome, and hyperplastic polyposis.[7,8,9]

Epidemiologic studies have shown that a personal history of colon adenomas places one at an increased risk of developing colon cancer.[10]

Two complementary interpretations of this observation are as follows:

  1. The adenoma may reflect an innate or acquired tendency of the colon to form tumors.
  2. Adenomas are the primary precursor lesion of colon cancer.

More than 95% of CRCs 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 CRCs arise from adenomas, adenocarcinomas are generally considered to arise from adenomas,[11,12,13,14,15] based upon the following important observations:

  1. Benign and malignant tissue occur within colorectal tumors.[16]
  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.[17]
1|2|3|4|5|6|7|8

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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