Lynch syndrome genetics and clinical implications

Abstract

Lynch syndrome (LS) is one of the most prevalent hereditary cancer syndromes in man and accounts for some 3% of unselected patients with colorectal or endometrial cancer and 10–15% of those with DNA mismatch repair (MMR)-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 revolutionized the treatment of advanced cancers with MMR defects. We aim to review the recent progress in the LS field and discuss how the accumulating epidemiological, clinical, and molecular information have contributed to a more accurate and complete picture of LS, resulting in genotype- and immunological subtype-specific strategies for surveillance, cancer prevention, and treatment.