MUTYH and colorectal carcinoma: While germline mutations in APC, the mismatch repair (MMR) genes, MUTYH/MYH, SMAD4, ALK3 and STK11/LKB1 confer a high risk of CRC, collectively, such mutations account for <5% of disease (Aaltonen et al, 2007) with much of the remaining variation in genetic risk likely to be explained by combinations of more common, lower penetrance variants.