Prediction of Germline Mutations and Cancer Risk in the Lynch Syndrome

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Abstract
The Lynch syndrome (ie, hereditary nonpolyposis colorectal cancer [HNPCC]) is the most common familial colorectal cancer (CRC).1,2 It can be caused by germline deleterious mutations of DNA mismatch repair (MMR) genes, including MLH1,3,4MSH2,5MSH6,6 and several others.7 Screening for individuals likely to carry a deleterious mutation of these genes has traditionally relied on examination of family history, as per the Amsterdam Criteria,8-10 and has recently moved toward multistep algorithms combining family history with molecular tumor characteristics such as microsatellite instability (MSI),11 as per the Bethesda Guidelines.2,12