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

Table 1. Estimated Relative and Absolute Risk of Developing Colorectal Cancer (CRC) continued...

Hereditary CRC has two well-described forms: FAP (including an attenuated form of polyposis [AFAP]), due to germline mutations in the APC gene,[53,54,55,56,57,58,59,60] and Lynch syndrome (LS) (also called hereditary nonpolyposis colorectal cancer [HNPCC]), which is caused by germline mutations in DNA MMR genes.[61,62,63,64] Many other families exhibit aggregation of CRC and/or adenomas, but with no apparent association with an identifiable hereditary syndrome, and are known collectively as familial CRC.[2]

Difficulties in Identifying a Family History of CRC Risk

The accuracy and completeness of family history data must be taken into account in using family history to assess individual risk in clinical practice, and in identifying families appropriate for cancer research. A reported family history may be erroneous, or a person may be unaware of relatives with cancer.[65] In addition, small family sizes and premature deaths may limit how informative a family history may be. Also, due to incomplete penetrance, some persons may carry a genetic predisposition to CRC but do not develop cancer, giving the impression of skipped generations in a family tree.

Accuracy of patient-reported family history of colon cancer has been shown to be good, but it is not optimal. Patient report should be verified by obtaining medical records whenever possible, especially for reproductive tract cancers that may be relevant in identifying risk of LS. (Refer to the Accuracy of the Family History section in the PDQ summary on Cancer Genetics Risk Assessment and Counseling for more information.)

Other Risk Factors for CRC

Other risk factors that may influence the development of adenomatous polyps and CRC risk include diet, use of nonsteroidal anti-inflammatory drugs (NSAIDs), postmenopausal hormone use, cigarette smoking, colonoscopy with removal of adenomatous polyps, and physical activity. Even in LS, a hereditary form of colon cancer, cigarette smoking has been identified as a risk factor for the development of colorectal adenomas.[66] (Refer to the Lynch Syndrome [LS] section of this summary for more information).

(Refer to the PDQ Summary on Prevention of Colorectal Cancer for more information.)

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