Beyond HRR defects, disruptions in mismatch repair (MMR) pathway genes, like MLH1, MSH2, MSH6, and PMS2, compromise DNA replication error correction, leading to microsatellite instability (MSI), a hallmark of Lynch syndrome–associated cancers, promoting genomic instability and tumorigenesis (31) (Figure 1). This evidence concerns the gene MSH2 and cancer.