Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p < 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.
Keywords: CRC; Lynch syndrome; extracolonic tumors; mismatch repair gene.