Which of the following genes are associated with Lynch syndrome and are primarily involved in DNA mismatch repair?

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is primarily linked to defects in DNA mismatch repair (MMR) genes. The correct answer includes MLH1, MSH2, MSH6, and PMS2, which are all integral components of the MMR system.

MLH1 and MSH2 are the most commonly mutated genes in Lynch syndrome and are essential for the repair of DNA replication errors. When these genes are mutated, it leads to microsatellite instability, a hallmark of Lynch syndrome, and increases the risk for various cancers, particularly colorectal and endometrial cancers. MSH6 and PMS2 further contribute to this pathway, with MSH6 acting as a partner to MSH2 in recognizing mismatches, while PMS2 is part of the endonuclease complex that activates repair of the detected errors.

Understanding these genetic components highlights the critical role of DNA repair in cancer prevention. By identifying mutations in these genes, individuals at high risk can be monitored more closely for malignancies associated with Lynch syndrome.