Impact of Mutations in DNA Repair Genes in Lynch Syndrome: A Systematic Literature Review

Introduction: Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer, is a genetic condition that significantly increases the risk of developing colorectal cancer and other types of cancer. This syndrome is caused by mutations in DNA repair (MMR) genes, which are responsible for correcting errors that occur during DNA replication. Methodology: Scientific databases such as PubMed, Scopus, and Web of Science were consulted for this systematic review. Studies that addressed mutations in MMR genes (MLH1, MSH2, MSH6, PMS2 and EPCAM) and their association with Lynch syndrome were included. Studies that did not present relevant clinical data or that were not systematic reviews were excluded. Results: The results showed that mutations in MMR genes are responsible for approximately 1-7% of all cases of colorectal cancer. The most common mutations are found in the MLH1 (50%) and MSH2 (40%) genes, while MSH6, PMS2 and EPCAM represent a smaller proportion1. These mutations lead to genomic instability, resulting in a high rate of mutations in tumour cells, which contributes to the development of cancer. Conclusion: The systematic review demonstrated that mutations in DNA repair genes have a significant impact on Lynch Syndrome, increasing the risk of colorectal cancer and other types of cancer. Identifying these mutations is crucial for early diagnosis and implementation of screening and prevention programs. Furthermore, understanding the molecular basis of the syndrome may lead to the development of new targeted therapies.