MRC1 and Lynch syndrome: Traditional definitions, which rely on family history and age at disease onset, suggest that Lynch syndrome may account for about 5% of CRC cases.127 However, more rigorous methodologies, such as molecular, histological, and immunohistochemical analyses, suggest that when Lynch syndrome is strictly defined by the presence of a germline MMR mutation, the percentage drops to approximately 2.5%.128 The variability in the estimated prevalence across studies may be attributable to differences in genetic or environmental factors or the methodologies employed.