Infrequent mutations of the hOGG1 gene, that is involved in the excision of 8-hydroxyguanine in damaged DNA, in human gastric cancer.
DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh8Gua), which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9 gastric cancer cell lines and 35 primary gastric cancers for mutations and genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single strand conformation polymorphism analysis. A G-to-A transition was detected in a gastric cancer cell line, MKN1. This nucleotide change caused the conversion of the amino acid from Arg to His at codon 154, which is located in a domain highly conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected in primary gastric cancers. We compared the distribution of the polymorphic alleles associated with enzymatic activity (hOGG1-Ser326 vs. hOGG1-Cys326) between 35 gastric cancer patients and 42 healthy individuals. Although the frequency of the Cys326 allele, associated with low enzymatic activity, in gastric cancer patients was a little higher than that in healthy individuals, the difference did not reach statistical significance. These results suggest that low hOGG1 activity due to mutations and genetic polymorphisms is involved in the development of only a small subset of gastric cancers.
Biology Division, National Cancer Center Research Institute, Tokyo.
K
K
Shinmura
T
T
Kohno
H
H
Kasai
K
K
Koda
H
H
Sugimura
J
J
Yokota
D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
C024829:8-hydroxyguanine; D006147:Guanine; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase