In these studies, colorectal surveillance by colonoscopy, performed at major clinical academic institutions worldwide, has failed to prevent colorectal cancer (CRC) in carriers of pathogenic variants in the mismatch repair genes MLH1, MSH2 and MSH6. In PLSD, we calculated the lifetime risk of CRC in carriers from 25 to 75 years of age who were receiving colonoscopic surveillance as 43–46% for path_MLH1 and path_MSH2 [5]. The gene discussed is MLH1; the disease is colorectal carcinoma.