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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...

    Identification of persons at high genetic risk of CRC

    Clinical criteria may be used to identify persons who are candidates for genetic testing to determine whether an inherited susceptibility to CRC is present. These criteria include the following:

    • A strong family history of CRC and/or polyps (especially oligopolyposis).
    • Multiple primary cancers in a patient with CRC.
    • Existence of other cancers within the kindred consistent with known syndromes causing an inherited risk of CRC, such as endometrial cancer.
    • Early age at diagnosis of CRC.

    When such persons are identified, options tailored to the patient situation are considered. (Refer to the Major Genetic Syndromes section of this summary for information on specific interventions for individual syndromes.)

    At this time, the use of mutation testing to identify genetic susceptibility to CRC is not recommended as a screening measure in the general population. The rarity of mutations in the APC tumor suppressor gene and LS-associated MMR genes and the limited sensitivity of current testing strategies render general population testing potentially misleading and not cost effective.

    Rather detailed recommendations for surveillance in FAP and LS have been provided by several organizations representing various medical specialties and societies. The following guidelines are readily available through the National Guideline Clearinghouse:

    • American Cancer Society.[70]
    • United States Multisociety (American Gastroenterological Association and American Society for Gastrointestinal Endoscopy) Task Force on Colorectal Cancer.[71]
    • American Society of Colon and Rectal Surgeons.[72]
    • National Comprehensive Cancer Network.[73]
    • Gene Reviews.

    The evidence bases for recommendations are generally included within the statements or guidelines. In many instances, these guidelines reflect expert opinion resting on studies that are rarely randomized prospective trials.

    Primary Prevention of Familial CRC

    Chemoprevention

    Observational studies of average-risk people have suggested that the use of some drugs and supplements (NSAIDs, estrogens, folic acid, and calcium) might prevent the development of CRC.[74] (Refer to the PDQ summary on Prevention of Colorectal Cancer for more information.) None of the evidence is convincing enough to lead expert groups to recommend these drugs and supplements specifically to prevent CRC, and few studies specifically enrolled people with an inherited predisposition for CRC. Although antioxidants are hypothesized to prevent cancer, a randomized controlled trial of antioxidant vitamins (beta carotene, vitamin C, and vitamin E) has shown no effect on CRC incidence.[75]

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