There was no significant association between OGG1Ser326Cys polymorphism and CRC, but the homozygous Cys/Cys variant genotype was associated with an increased risk of colon cancer (p<0.05).
We describe here the first pathogenic germline mutation in OGG1, a splice site mutation affecting exon 1, which was inherited from the father, in combination with a maternal MUTYH missense mutation p.Ile223Val in a female patient with advanced synchronous colon cancer and adenomas at the age of 36 years pointing towards digenic inheritance for colorectal cancer (CRC) predisposition.
In a study of 1,604 incident colon cancer cases and 1,969 matched population-based controls genotyped for BER variants OGG1 (S326C) and XRCC1 (R194W, R280H, and R399Q), we found no associations with colon cancer overall.
Case-control studies of genetic polymorphisms in DNA repair enzymes suggest that the common variant Ser326Cys in OGG1 may be a risk factor for lung cancer, whereas a rare variant in OGG1 and germ line mutations in the corresponding mismatch repair gene MYH are risk factors for hereditary colon cancer.
In studies that explored potential interactions with environmental factors, cancer risk for hOGG1 genotypes differed depending on exposure, especially for colon cancer.
These results suggest that the hOGG1Ser326Cys polymorphism is probably not a major contributor to individual colon cancer susceptibility overall, but the Cys/Cys genotype may alter the impact of some environmental factors on colon cancer development.