Course : MOC Part IV: Assessment for and Management of Lynch Syndrome

Lynch syndrome, also referred to as hereditary non-polyposis colon cancer (HNPCC), is a hereditary cancer predisposition syndrome whose main cancer risks are colorectal cancer and endometrial cancer. Although the terms Lynch syndrome and HNPCC are often used interchangeably, a classification of Lynch syndrome specifically refers to families whose cancers are due to an mutation in one of several mismatch repair genes. The lifetime risk for colorectal is as high as 75% by the age of 70 years with up to a 52% risk of a second colorectal cancer if appropriate screening is not implemented. The endometrial cancer risk is 27-60%. Additional lifetime cancer risks that are within the spectrum of Lynch syndrome are ovarian (6-12%), urothelial, and gastric (5-6%). Less common cancers include hepatobiliary tract, brain, small bowel, pancreatic, sebaceous adenomas or carcinomas, and keratocanthomas.


Germline mutations in the DNA mismatch repair (MMR) genes are responsible for the hereditary risk. MLH1 and MSH2 mutations account for 70-90% of Lynch syndrome families, MSH6 and PMS2 are responsible for 7-10% and approximately 5% of Lynch syndrome families respectively. All together, Lynch syndrome represents 1–3% of colorectal cancers and 1–4% of endometrial cancers. Thus, appropriate identification and assessment for Lynch syndrome is imperative for proper management.

Techniques employed to assess the possibility of Lynch syndrome include microsatellite instability (MSI), immunohistochemical (IHC). Germline analysis of the MMR genes may be used to identify the specific gene mutation, when a diagnosis is suspected based upon family history or molecular evidence of an underlying problem in a MMR gene.

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