title: Functional polymorphisms of the hOGG1 gene confer risk to type 2 epithelial ovarian cancer in Chinese.
abstract: OBJECTIVE
  8-Hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside that can lead to misincorporation of bases. Human 8-oxoguanine DNA glycosylase (hOGG1) is the key defense enzyme against mutation by the cellular 8-OHdG in duplex DNA. The present study was aimed to explore whether the hOGG1 gene variants play an important role in the carcinogenesis of epithelial ovarian cancer (EOC).
  
  
  METHODS
  Germ line variants in 5'-untranslated region (c.-18G>T, c.-23A>G, c.-45G>A, and c.-53G>C) and c.977C>G (Ser326Cys) polymorphism in exon7 of the hOGG1 gene in 420 sporadic EOCs and 840 controls were detected. Immunohistochemical and promoter luciferase activity assays were used to explore the effect of c.-18G>T variant on hOGG1 expression.
  
  
  RESULTS
  In contrast to type I EOC cases, patients with type II EOC were usually older, already in the advanced stage, and exhibited a common protein 53 (p53) overexpression. The frequencies of genotypes c.-18G/T and c.977G/G in hOGG1 were significantly high in the patients with type II EOC (odds ratio, 2.83; 95% confidence interval, 1.45-5.52; odds ratio, 1.66; 95% confidence interval, 1.26-2.17) but not in the patients with type I EOC. The average level of hOGG1 protein in the normal tissues adjacent to the type II EOC-carried c.-18G/T was lower than that with c.-18G/G (P = 0.01). The luciferase activity in the c.-18T allele was lower than that in the c.-18G allele (P = 0.001).
  
  
  CONCLUSIONS
  The genotypes of c.-18G/T in 5'-untranslated region and c.977G/G in exon7 of the hOGG1 gene would confer risk to type II EOC.
authors: Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.
authors: Xiaoxiang
authors: X
authors: Chen
authors: Xiufang
authors: X
authors: Liu
authors: Jingmei
authors: J
authors: Wang
authors: Wenwen
authors: W
authors: Guo
authors: Caixia
authors: C
authors: Sun
authors: Zhenming
authors: Z
authors: Cai
authors: Qiang
authors: Q
authors: Wu
authors: Xia
authors: X
authors: Xu
authors: Yaping
authors: Y
authors: Wang
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002681:China; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D020121:5' Untranslated Regions; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human