Genetic testing by cancer site: colon (nonpolyposis syndromes)

Lynch syndrome, which is associated with mutations in 1 of 4 mismatch repair genes (MLH1, MSH2, MSH6, and PMS2), is a well-described hereditary cancer predisposition syndrome associated with a substantial risk of colon, rectum, and endometrial cancer. Historically, individuals with Lynch syndrome were identified using clinical classification criteria that have since been shown to be ineffective in most clinical settings, giving way to a more molecular diagnostic approach. These techniques have been repeatedly discussed in the literature, and there are multiple considerations in determining the best approach for a specific family. We review these approaches here as well as the clinical presentation of Lynch syndrome. Although still a relatively rare condition, we stress the importance of the identification of individuals with Lynch syndrome, given the clear data that predictive testing of at-risk family members and subsequent screening for cancers can reduce mortality associated with colorectal and endometrial cancer in these families.