Lynch syndrome and colorectal cancer: A review of current perspectives in molecular genetics and clinical strategies

Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is an inherited condition associated with a higher risk of colorectal cancer (CRC) and other cancers. It is caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6 and PMS2. These mutations lead to microsatellite instability (MSI) and defective DNA repair mechanisms, resulting in increased cancer risk. Early detection of LS is crucial for effective management and cancer prevention. Endoscopic surveillance, particularly regular colonoscopy, is recommended for individuals with LS to detect CRC at early stages. Additionally, universal screening of CRC for MMR deficiency can help identify at-risk individuals. Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis, making informed decisions regarding surveillance and prevention, and offering reproductive options to reduce the transmission of pathogenic variants of the offspring. The aim of this review is to outline current strategies for the diagnosis, surveillance, and management of LS, with a focus on the role of genetic counseling, endoscopic screening, and emerging therapeutic approaches to mitigate cancer risk in affected individuals.