Furthermore, a digenic inheritance model was proposed once before for CRC predisposition in a carrier of variants in the oxidative DNA damage repair genes MUTYH and OGG1. 17Although the functional evidence of combined defects in oxidative DNA damage repair genes is still lacking, the coinheritance of MSH6 and MUTYH variants in at least three, but likely five cancer cases within one family warrants further mechanistic and clinical studies. This evidence concerns the gene MSH6 and colorectal carcinoma.