Genetic testing in gastroenterology: Lynch syndrome

Abstract

Lynch syndrome/Hereditary non-polyposis colorectal cancer is caused by inherited germline mutations in mismatch repair (MMR) genes, and accounts for 2-5% of colorectal cancers (CRC) . It is characterized by young onset CRC and an increased risk for gynaecologic, urinary tract and gastrointestinal cancers. Family history evaluation is crucial in the early identification of individuals at risk for Lynch syndrome. Individuals whose family history includes multiple relatives with cancer, two or more primary cancers, or component tumours diagnosed at a young age, should undergo genetic evaluation for Lynch syndrome. Guidelines recommend initial evaluation of the tumour with immunohistochemistry or microsatellite instability testing followed by germline testing for mutations in MMR genes in those with abnormal results. Genetic test results can guide screening recommendations for patients and their families. However, results are not always conclusive and in such cases recommendations for cancer screening should be individualized on the basis of personal and family history.