Lynch syndrome is the most common cause of inherited colorectal cancer (CRC). It is characterized by a significantly increased risk for CRC and endometrial cancer as well as a risk of several other malignancies. This topic will review the genetic basis, clinical manifestations, and diagnosis of Lynch syndrome. Surveillance strategies for individuals with Lynch syndrome are discussed separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management of patients and families".)
●Hereditary nonpolyposis colorectal cancer (HNPCC) refers to patients and/or families who fulfill the Amsterdam I or II criteria for Lynch syndrome (table 1). (See 'Amsterdam criteria' below.)
●Lynch syndrome refers to patients and families with a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) or the EPCAM gene.
Approximately 70 to 80 percent of patients with colorectal cancer (CRC) have sporadic disease, but the remaining 20 to 30 percent have a familial or inherited component that might be causative. Lynch syndrome is the most common inherited CRC susceptibility syndrome and accounts for approximately 3 percent of newly diagnosed cases of CRC and 2 percent of endometrial cancer.
Lynch syndrome is an autosomal dominant disorder that is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes or loss of expression of MSH2 due to deletion in the EPCAM gene (previously called TACSTD1). The MMR genes that are associated with Lynch syndrome include: