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Cancer Health Center

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

Table 10. Clinical Practice Guidelines for Colon Surveillance of BiallelicMYH-Associated Polyposis (MAP) continued...

Prostate cancer was found to be associated with LS in a study of 198 families from two U.S. LS registries in which prostate cancer had not originally been part of the family selection criteria. Prostate cancer risk in relatives of MMR gene mutation carriers was 6.3% at age 60 years and 30% at age 80 years, versus a population risk of 2.6% at age 60 years and 18% at age 80 years, with an overall hazard ratio of 1.99 (95% CI, 1.31-3.03). Notwithstanding prevalent controversy surrounding routine prostate-specific antigen (PSA) screening, the authors suggested that screening by means of PSA and digital rectal exam (DRE) beginning at age 40 years in male MMR gene carriers would be "reasonable to consider."[245]

Another study assessed a series of 114 adrenocortical carcinomas (ACCs). Of 94 patients who had a detailed family history assessment and in whom Li-Fraumeni syndrome testing was nondiagnostic, 3 patients had family histories that were suggestive of LS. The prevalence of MMR gene mutations in 94 families was 3.2%, similar to proportion of LS among unselected colorectal and endometrial cancer patients. In a retrospective review of 135 MMR gene mutation-positive LS families from the same program, two probands were found to have had a history of ACC. Of the four ACCs in which MSI testing could be performed, all were microsatellite stable (MSS). These data suggest that if LS is otherwise suspected in an ACC index case, an initial evaluation of the ACC using MSI or IHC testing may be misleading.[244]

Muir-Torre syndrome is considered a variant of LS and includes a phenotype of multiple cutaneous neoplasms (including sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas). The skin lesions and CRC define the phenotype,[251,252] and clinical variability is common. Both mutations in the MSH2 and MLH1 genes have been found in Muir-Torre families.[253,254,255] A study of 1,914 MSH2 and MLH1 unrelated probands found MSH2 to be more common in individuals with the Muir-Torre syndrome phenotype.[256]

Historical criteria for defining LS families

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