title: OGG1 Cys326 variant, allelic imbalance of chromosome band 3p25.3 and TP53 mutations in ovarian cancer.
abstract: A Ser326Cys amino acid variant encoded by OGG1 that removes the highly mutagenic 8-oxo-7,8-dihydroguanine adducts resulting from the oxidative damage produced by reactive oxygen species, has been suggested to reduce activity of the enzyme and result in an increase in G:C --> T:A transversions. Carriers homozygous for the Cys326 variant have been associated with increased risk in some cancers. In this study, we tested the association of this polymorphism with epithelial ovarian cancer (EOC) (n=91 cases) in comparison with women unaffected by the disease (n=57). Although the genotype encoding the homozygous Cys326 variant was found more often in cases (11%) than controls (9%), this was not statistically significant (p=0.297). As OGG1 at chromosome band 3p25.3 overlaps a region exhibiting allelic imbalance (AI) in EOC, we also examined the frequency of AI of the OGG1 locus and its association with somatic mutations in the TP53 tumor suppressor gene, which is frequently mutated in EOC. The frequency of AI and TP53 mutations in EOC was 32 and 37%, respectively. Although the proportion of EOC cases harboring the genotype homozygous for Cys326 was greater in TP53 mutation-positive cases (5 of 34, 15%) than mutation-negative cases (5 of 57, 9%), the distribution of genotypes was not significantly different (p=0.289). Four of the six heterozygous Ser326/Cys326 samples exhibiting AI, displayed loss of the Ser326 variant. About 16% of samples exhibited both AI of the OGG1 locus and a TP53 mutation. Proportionately more EOC samples harbored a mutation in the group of samples exhibiting AI (15 of 29, 52%) in comparison to the group of samples with no AI (19 of 62, 31%) (p=0.036). Although the OGG1 Cys326 variant appears to play a minor role in conferring increased risk of ovarian cancer, the observed AI of the OGG1 locus in association with TP53 somatic mutations warrants further investigation in this disease.
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal H3G 1A4, Canada.
authors.forename: Suzanna L
authors.initials: SL
authors.lastname: Arcand
authors.forename: Diane
authors.initials: D
authors.lastname: Provencher
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
mesh_terms: D022981:Allelic Imbalance; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human