MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas

초록

This study was done to characterize base excision repair (BER) genes and adenomatous polyposis coli (APC) alterations in the tumorigenesis of multiple colorectal adenomas in Korean patients. In total, 217 adenomas (mean number = 10) and 117 cancers were available from 143 patients. The heterozygous genotype of OGG1 c.1-18G > T was closely associated with multiple adenoma families (P < 0.001), while MYH A359V mutation exhibited a tendency (P = 0.053). MYH R170G mutation was exclusively identified in one patient. The G:C > T:A transversion or attenuated familial adenomatous polyposis (AFAP) mutations of APC was identified in the specific genotypes of BER variants. Tubular adenomas or adenomas with none-to-mild dysplasia were significantly associated with polymorphic genotypes of OGG1 IVS4-15 and S326C. In addition, large and pedunculated adenomas were more frequent in patients with G:C > T:A transversion and AFAP mutations of APC, respectively. However, BER variants were not associated with mismatch repair or altered p53 protein expression. Conclusively, two novel mutations of MYH and a novel OGG1 polymorphism seemed to be associated with multiple colorectal adenomas in Korean families, differing from those in other ethnic groups. Some BER variants involved in specific APC mutations are associated with characteristics of histogenesis other than altered mismatch repair or p53 pathway.

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