To investigate the role of a defective 8-oxo-G repair we performed a germline mutation screening in the genes OGG1, MTH1 and MUTYH, in 81 patients with a clinical phenotype ranging from attenuated or atypical adenomatous polyposis coli including hyperplastic polyps to hereditary non-polyposis colorectal cancer (HNPCC) type X syndrome without mono- or biallelic mutations in either APC, MUTYH or the DNA mismatch repair genes.
MYH, OGG1 and MTH1 are members of base excision repair (BER) families, and MYH germline mutations were recently identified in patients with multiple adenomas or familial adenomatous polyposis (FAP).
Accumulation of multiple genetic alterations are involved in the tumorigenesis of CC, of which genetic alterations of APC and DCC occur at a relatively early stage, and of OGG1 and p53 occur at a relatively late stage during development of CC.