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Recently identified colon cancer predispositions: MYH and MSH6 mutations.

Single-gene germline mutations conferring a high lifetime risk of colorectal cancer (CRC) account for up to 6% of all CRC cases. The most widely studied monogenic colorectal cancer syndromes include familial adenomatous polyposis (FAP) and Lynch syndrome. However, additional syndromes continue to be defined and new predisposition genes are continuing to be identified. Most recently, MYH-associated polyposis (MAP) and an "atypical Lynch syndrome" related to the presence of MSH6 mutations have been linked to an increased risk of CRC. In this review, we summarize basic information related to these newly recognized gene mutations, including the accumulating data on the prevalence and penetrance of deleterious mutations, as well as the management options for identified carriers and their families. Recognizing these heritable syndromes is essential and predictive genetic testing will continue to transform the field of cancer risk assessment by offering the opportunity to focus on more precise risk management and cancer prevention.