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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...

The EGAPP analysis made several assumptions, including (1) IHC and MSI will not detect all LS patients and (2) not all patients with CRC will opt for testing.

Results are available from a Markov model that incorporated the risks of colorectal, endometrial, and ovarian cancers to estimate the effectiveness and cost-effectiveness of strategies to identify LS among persons with newly diagnosed CRC.[357] The strategies incorporated in the model were based on clinical criteria, prediction algorithms, and tumor testing or up-front germline mutation testing followed by directed screening and risk-reducing surgery. Similar to the EGAPP working group, IHC followed by BRAF mutation testing was the preferred strategy in this study. An incremental cost-effectiveness ratio of $36,200 per life year gained resulted from this strategy. In this model, the number of relatives tested (3 to 4) per proband was a critical determinant of both effectiveness and cost-effectiveness.

A different approach based on risk assessments of 100,000 simulated individuals representative of the U.S. population who were tracked from age 20 and exposed to 20 different screening strategies has been reported.[358] In this study, the strategies involved risk assessment at different ages utilizing the PREMM126 model followed by mutation analysis for MLH1, MSH2, MSH6, and PMS2 in individuals whose mutation risk threshold exceeded 0%, 2.5%, 5%, or 10%. In individuals whose risk assessment (starting at age 25, 30, or 35 years) for carrying a mutation exceeded 5%, colorectal and endometrial cancers in mutation carriers were reduced by 12.4% and 8.8%, respectively. In the whole population, this strategy increased the quality adjusted life-years by 135 years per 100,000 individuals with an average cost-effectiveness ratio of $26,000. The authors suggested that the outlined strategy was more cost effective than current practice and could improve health care outcomes.

Recognizing the controversial conclusions of the EGAPP working group, the Centers for Disease Control and Prevention convened a special meeting of cancer genetics experts to critique these recommendations. The group concluded that "genetic screening of all newly diagnosed CRC cases for LS (universal LS screening) can theoretically result in population health benefits, and feasibility has been demonstrated."[359]

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