Lynch Syndrome 101 (Years, That Is)

Abstract

Lynch syndrome was described over a century ago but information on the medical consequences and optimal management of this disorder continue to amass and evolve. This brief overview highlights the gene-specific and site-specific cancer penetrance and management options for those with Lynch syndrome.KEY POINTSLynch syndrome is an autosomal dominant predisposition for specific cancers caused by the presence of a germline mutation that disturbs the function of a DNA mismatch repair gene.When a second hit occurs in a mismatch repair gene with the germline mutation, the ground is laid for an accelerated accumulation of mutations in key tumor suppressor genes and oncogenes.Tumor microsatellite instability is the phenotype of defective DNA mismatch repair, but is caused by Lynch syndrome in only a minority of cases.There is good evidence that colonoscopic screening for colorectal cancer reduces colorectal cancer deaths, that hysterectomy/bilateral oophorectomy reduces endometrial/ovarian cancers, and that more extensive colonic resection when colorectal cancer is diagnosed reduces the risk of subsequent colon cancers.Chemoprevention with aspirin may be a potent intervention in the prevention of colorectal cancer and other Lynch syndrome-related cancers, according to a single large randomized controlled trial.