Lynch Syndrome Genetics and Clinical Implications

Lynch syndrome (LS) is one of the most prevalent hereditary cancer syndromes in humans and accounts for some 3% of unselected patients with colorectal or endometrial cancer and 10%-15% of those with DNA mismatch repair-deficient tumors. Previous studies have established the genetic basis of LS predisposition, but there have been significant advances recently in the understanding of the molecular pathogenesis of LS tumors, which has important implications in clinical management. At the same time, immunotherapy has revolu-tionized the treatment of advanced cancers with DNA mismatch repair defects. We aim to review the recent prog-ress in the LS field and discuss how the accumulating epidemiologic, clinical, and molecular information has contributed to a more accurate and complete picture of LS, resulting in genotype-and immunologic subtype-specific strategies for surveillance, cancer prevention, and treatment. MMR genes (or EPCAM), and the term LS is currently restricted to cases fulfilling this molecular definition.