Mutational analysis ofOGG1,MYH,MTH1in FAP, HNPCC and sporadic colorectal cancer patients: R154HOGG1polymorphism is associated with sporadic colorectal cancer patients.

MYH,OGG1andMTH1are members of base excision repair (BER) families, andMYHgermline mutations were recently identified in patients with multiple adenomas or familial adenomatous polyposis (FAP). A total of 20APC-negative Korean FAP patients were analyzed forOGG1,MYHandMTH1germline mutations. A total of 19 hereditary nonpolyposis colorectal cancer (HNPCC), 86 suspected HNPCC, and 246 sporadic colorectal cancer cases were investigated forOGG1andMYHmutations. A total of 14 R154HOGG1polymorphisms were identified in hereditary, sporadic colorectal cancers, and normal controls. For the case-control analysis ofOGG1R154H, a total of 625 hereditary or sporadic colorectal cancer patients and 527 normal controls were screened. R154H was a rare polymorphism associated with sporadic colorectal cancer patents (OR: 3.586,P= 0.053). R154H does not segregate with cancer phenotypes. Upon examining the possibility of recessive inheritance of R154H, we could not identify any complementary mutations inOGG1,MYHorMTH1. Samples with R154H were further screened for mutations ofK-ras,ß-catenin,APC,p53,BRAFand the microsatellite instability (MSI) status. Eight somatic mutations were identified in these genes and G:C to T:A transversion mutations were not dominant in samples harboring R154H. This result raises the possibility thatOGG1R154H may function as a low/moderate-penetrance modifier for colorectal cancer development. [ABSTRACT FROM AUTHOR]