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Functional Polymorphisms of the hOGG1 Gene Confer Risk to Type 2 Epithelial Ovarian Cancer in Chinese
  1. Xiaoxiang Chen, MD*,,,
  2. Xiufang Liu, PhD*,,
  3. Jingmei Wang, MD*,,§,
  4. Wenwen Guo, PhD*,,
  5. Caixia Sun, PhD*,,
  6. Zhenming Cai, PhD*,,
  7. Qiang Wu, MD,
  8. Xia Xu, MD and
  9. Yaping Wang, MD*,
  1. *Department of Medical Genetics,
  2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, China;
  3. Department of Gynecologic Oncology, Jiangsu Institute of Cancer Research, Nanjing, China;
  4. §Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China; and
  5. Department of Chemotherapy, Jiangsu Institute of Cancer Research, Nanjing, China.
  1. Address correspondence and reprint requests to Yaping Wang, MD, The Department of Medical Genetics, Nanjing University School of Medicine, 22 Hankou Rd, Nanjing 210093, China. E-mail: wangyap{at}nju.edu.cn.

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).

Conclusion: 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.

  • hOGG1 gene
  • 5′-UTR
  • Epithelial ovarian cancer
  • Single nucleotide polymorphism

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Footnotes

  • This work was partly supported by the National Natural Science Foundation of China (grant numbers 81070273 and 30972535); the Doctoral Foundation of Education Ministry of China (grant number 20070284015); Natural Science Foundation of Jiangsu Province, China (grant number BK2008269); and the Jiangsu Province Institute of Cancer Research Foundation (grant number ZQ200703).

  • This is an original article we wish to be regarded as "epidemiologic study on ovarian cancer."

  • The authors declare that there is no conflict of interest.

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