Lynch syndrome: history, causes, diagnosis, treatment and prevention (CAPP2 trial).

Hereditary cancer due to pathological mutations in the mismatch repair gene family is now known as Lynch syndrome and affects at least 1 in 1,000 people, resulting in a 30-50% cancer risk most often involving the colorectum and endometrium. Annual or biennial colonoscopy reduces cancer deaths and many offer gynaecological surveillance, but most other associated cancers are not amenable to early detection. As microsatellite instability testing and tumour immunohistochemistry become routine, case finding will improve. Our recent demonstration that 600 mg aspirin per day for at least 2 years reduces the cancer burden by 63% after a 3-year lag period reinforces the need to identify gene carriers and introduce them to chemoprevention. CaPP3 will test different doses of aspirin in at least 3,000 gene carriers to determine whether low-dose aspirin is as effective.