Breast Cancer Research and Treatment

, Volume 122, Issue 3, pp 835–842 | Cite as

The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis

  • Weiguang Yuan
  • Lidan Xu
  • Yuanxi Feng
  • Yue Yang
  • Wangyang Chen
  • Jingwei Wang
  • Da Pang
  • Dianjun Li


It was reported that the functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase gene was associated with breast cancer risk; however, the published studies have inconsistent conclusions. To elucidate the effect of hOGG1 Ser326Cys on the susceptibility to breast cancer, all available studies were collected in this meta-analysis. We extracted the data from 10 case–control studies that were published in the PubMed database from 2003 to 2008 using the search phrases “human 8-oxoguanine DNA glycosylase, hOGG1, OGG1, OGG, polymorphism, genetic variation, and breast cancer.” This meta-analysis included 4,963 breast cancer cases and 4,776 control subjects. The results showed that individuals who carrying the hOGG1 326Cys allele in the additive model did not have significantly increased risk of breast cancer compared with those carrying the 326Ser allele (P = 0.47, OR = 1.02; 95% CI = 0.96–1.09); similarly, no significant association between the hOGG1 326Cys allele and breast cancer risk was found either in the recessive genetic model (P = 0.34, OR = 1.06; 95% CI = 0.94–1.18) for Cys/Cys versus Ser/Cys + Ser/Ser, or dominant genetic model (P = 0.78, OR = 1.01; 95% CI = 0.93–1.11) for Cys/Cys + Ser/Cys versus Ser/Ser. In the stratified analysis, the meta-analysis showed the association between hOGG1 326Cys allele in the additive model and breast cancer was significant in European subjects (P = 0.04, OR = 0.71; 95% CI = 0.51–0.98), and dominant genetic model (P = 0.004, OR = 0.44; 95% CI = 0.25–0.77). However, the association was not significant between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (Asians and Americans). The meta-analysis suggested that the hOGG1 326Cys allele plays a significant protective effect to breast cancer in European women.


hOGG1 SNP Breast cancer Meta-analysis 



All authors read and approved the final article. We are grateful to the members of the Institute of Cancer Prevention and Treatment of Harbin Medical University for supporting our study.


  1. 1.
    Sangrajrang S, Schmezer P, Burkholder I, Waas P, Boffetta P, Brennan P, Bartsch H, Wiangnon S, Popanda O (2008) Polymorphisms in three base excision repair genes and breast cancer risk in Thai women. Breast Cancer Res Treat 111:279–288CrossRefPubMedGoogle Scholar
  2. 2.
    Goode EL, Ulrich CM, Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11:1513–1530PubMedGoogle Scholar
  3. 3.
    Janssen K, Schlink K, Gotte W, Hippler B, Kaina B, Oesch F (2001) DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326. Mutat Res 486:207–216PubMedGoogle Scholar
  4. 4.
    Rossner P Jr, Terry MB, Gammon MD, Zhang FF, Teitelbaum SL, Eng SM, Sagiv SK, Gaudet MM, Neugut AI, Santella RM (2006) OGG1 polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev 15:811–815CrossRefPubMedGoogle Scholar
  5. 5.
    Kohno T, Shinmura K, Tosaka M, Tani M, Kim SR, Sugimura H, Nohmi T, Kasai H, Yokota J (1998) Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene 16:3219–3225CrossRefPubMedGoogle Scholar
  6. 6.
    Weiss JM, Goode EL, Ladiges WC, Ulrich CM (2005) Polymorphic variation in hOGG1 and risk of cancer: a review of the functional and epidemiologic literature. Mol Carcinog 42:127–141CrossRefPubMedGoogle Scholar
  7. 7.
    Choi JY, Hamajima N, Tajima K, Yoo KY, Yoon KS, Park SK, Kim SU, Lee KM, Noh DY, Ahn SH et al (2003) hOGG1 Ser326Cys polymorphism and breast cancer risk among Asian women. Breast Cancer Res Treat 79:59–62CrossRefPubMedGoogle Scholar
  8. 8.
    Kim JI, Park YJ, Kim KH, Song BJ, Lee MS, Kim CN, Chang SH (2003) hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer. World J Gastroenterol 9:956–960PubMedGoogle Scholar
  9. 9.
    Xing DY, Tan W, Song N, Lin DX (2001) Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. Int J Cancer 95:140–143CrossRefPubMedGoogle Scholar
  10. 10.
    Sugimura H, Kohno T, Wakai K, Nagura K, Genka K, Igarashi H, Morris BJ, Baba S, Ohno Y, Gao C et al (1999) hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 8:669–674PubMedGoogle Scholar
  11. 11.
    Wikman H, Risch A, Klimek F, Schmezer P, Spiegelhalder B, Dienemann H, Kayser K, Schulz V, Drings P, Bartsch H (2000) hOGG1 polymorphism and loss of heterozygosity (LOH): significance for lung cancer susceptibility in a caucasian population. Int J Cancer 88:932–937CrossRefPubMedGoogle Scholar
  12. 12.
    Ito H, Hamajima N, Takezaki T, Matsuo K, Tajima K, Hatooka S, Mitsudomi T, Suyama M, Sato S, Ueda R (2002) A limited association of OGG1 Ser326Cys polymorphism for adenocarcinoma of the lung. J Epidemiol 12:258–265PubMedGoogle Scholar
  13. 13.
    Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C, Lacroix A, Labuda D, Sinnett D (2001) Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions. Int J Cancer 92:220–225CrossRefPubMedGoogle Scholar
  14. 14.
    Coombs NJ, Cronin KA, Taylor RJ, Freedman AN, Boyages J (2009) The impact of changes in hormone therapy on breast cancer incidence in the US population. Cancer Causes Control. doi: 10.1007/s10552-009-9437-5 PubMedGoogle Scholar
  15. 15.
    Jara-Lazaro AR, Thilagaratnam S, Tan PH (2010) Breast cancer in Singapore: some perspectives. Breast Cancer 17:23–28CrossRefPubMedGoogle Scholar
  16. 16.
    Giles GG, Bell R, Farrugia H, Thursfield V (2009) Decrease in breast cancer incidence following a rapid fall in use of hormone replacement therapy in Australia. Med J Aust 190:164 (author reply 164–165)PubMedGoogle Scholar
  17. 17.
    Synowiec E, Stefanska J, Morawiec Z, Blasiak J, Wozniak K (2008) Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients. Mutat Res 648:65–72PubMedGoogle Scholar
  18. 18.
    Cai Q, Shu XO, Wen W, Courtney R, Dai Q, Gao YT, Zheng W (2006) Functional Ser326Cys polymorphism in the hOGG1 gene is not associated with breast cancer risk. Cancer Epidemiol Biomarkers Prev 15:403–404CrossRefPubMedGoogle Scholar
  19. 19.
    Huang CS, Chen JJ, Yang SY, Cheng CW, Chern HD, Chang KJ, Wu PE, Shen CY (2004) Breast cancer risk associated with genotypic polymorphism of oxidative DNA damage repair genes—a multigenic study of base excision repair and transcription-coupled repair in cancer susceptibility. J Genet Mol Biol 15:116–136Google Scholar
  20. 20.
    Romanowicz-Makowska H, Smolarz B, Makowski M, Polac I, Pertynski T (2008) Ser326Cys polymorphism in DNA repair genes hOGG1 in breast cancer women. Pol J Pathol 59:201–204PubMedGoogle Scholar
  21. 21.
    Zhang Y, Newcomb PA, Egan KM, Titus-Ernstoff L, Chanock S, Welch R, Brinton LA, Lissowska J, Bardin-Mikolajczak A, Peplonska B et al (2006) Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 15:353–358CrossRefPubMedGoogle Scholar
  22. 22.
    Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826PubMedGoogle Scholar
  23. 23.
    Zintzaras E, Ioannidis JP (2005) Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol 28:123–137CrossRefPubMedGoogle Scholar
  24. 24.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMedGoogle Scholar
  25. 25.
    Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  26. 26.
    Vogel U, Nexo BA, Olsen A, Thomsen B, Jacobsen NR, Wallin H, Overvad K, Tjonneland A (2003) No association between OGG1 Ser326Cys polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 12:170–171PubMedGoogle Scholar
  27. 27.
    Siiteri PK, Simberg N, Murai J (1986) Estrogens and breast cancer. Ann N Y Acad Sci 464:100–105CrossRefPubMedGoogle Scholar
  28. 28.
    De CJ, De CC (1948) Estrogens in advanced cancer of the breast. Med Times 76:432–434Google Scholar
  29. 29.
    Li H, Hao X, Zhang W, Wei Q, Chen K (2008) The hOGG1 Ser326Cys polymorphism and lung cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 17:1739–1745CrossRefPubMedGoogle Scholar
  30. 30.
    Yamane A, Kohno T, Ito K, Sunaga N, Aoki K, Yoshimura K, Murakami H, Nojima Y, Yokota J (2004) Differential ability of polymorphic OGG1 proteins to suppress mutagenesis induced by 8-hydroxyguanine in human cell in vivo. Carcinogenesis 25:1689–1694CrossRefPubMedGoogle Scholar
  31. 31.
    Lee AJ, Hodges NJ, Chipman JK (2005) Interindividual variability in response to sodium dichromate-induced oxidative DNA damage: role of the Ser326Cys polymorphism in the DNA-repair protein of 8-oxo-7, 8-dihydro-2′-deoxyguanosine DNA glycosylase 1. Cancer Epidemiol Biomarkers Prev 14:497–505CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Weiguang Yuan
    • 1
    • 2
  • Lidan Xu
    • 3
  • Yuanxi Feng
    • 4
  • Yue Yang
    • 1
  • Wangyang Chen
    • 1
  • Jingwei Wang
    • 1
  • Da Pang
    • 1
    • 5
  • Dianjun Li
    • 1
    • 2
  1. 1.Institute of Cancer Prevention and TreatmentHarbin Medical UniversityHarbinChina
  2. 2.Department of ImmunologyHarbin Medical UniversityHarbinChina
  3. 3.Laboratory of Medical GeneticsHarbin Medical UniversityHarbinChina
  4. 4.Department of Medical OncologyThe Third Affiliated Hospital of Harbin Medical UniversityHarbinChina
  5. 5.Department of SurgeryThe Third Affiliated Hospital of Harbin Medical UniversityHarbinChina

Personalised recommendations