Skip to main content

Advertisement

SpringerLink
Log in

RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

RAD51 plays a key role in homologous recombination repair of double-stranded DNA breaks which may cause chromosomal breaks and genomic instability. We performed a meta-analysis of 9 epidemiological studies involving 13,241 cases and 13,203 controls that examined the association between RAD51 135G>C polymorphism and breast cancer. No significant association of RAD51 135G>C polymorphism with breast cancer was found in overall and European populations. However, after the studies which did not fulfill Hardy–Weinberg equilibrium were excluded, we observed an overall significant increased breast cancer risk (for the recessive model CC vs. GG/CG: OR = 1.35, 95% CI = 1.05–1.74, P heterogeneity = 0.06). In summary, our meta-analysis suggested the RAD51 135G>C polymorphism may contribute to breast cancer susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Henning W, Sturzbecher HW (2003) Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. Toxicology 193:91–109

    Article  CAS  PubMed  Google Scholar 

  2. Tsuzuki T, Fujii Y, Sakumi K, Tominaga Y, Nakao K, Sekiguchi M, Matsushiro A, Yoshimura Y, Morita T (1996) Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc Natl Acad Sci USA 93:6236–6240

    Article  CAS  PubMed  Google Scholar 

  3. Thacker J (2005) The RAD51 gene family, genetic instability and cancer. Cancer Lett 219:125–135

    Article  CAS  PubMed  Google Scholar 

  4. Richardson C (2005) RAD51, genomic stability, and tumorigenesis. Cancer Lett 218:127–139

    Article  CAS  PubMed  Google Scholar 

  5. Lose F, Lovelock P, Chenevix-Trench G, Mann GJ, Pupo GM, Spurdle AB (2006) Variation in the RAD51 gene and familial breast cancer. Breast Cancer Res 8:R26

    Article  PubMed  Google Scholar 

  6. Levy-Lahad E, Lahad A, Eisenberg S, Dagan E, Paperna T, Kasinetz L, Catane R, Kaufman B, Beller U, Renbaum P, Gershoni-Baruch R (2001) A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers. Proc Natl Acad Sci USA 98:3232–3236

    Article  CAS  PubMed  Google Scholar 

  7. Wang WW, Spurdle AB, Kolachana P, Bove B, Modan B, Ebbers SM, Suthers G, Tucker MA, Kaufman DJ, Doody MM, Tarone RE, Daly M, Levavi H, Pierce H, Chetrit A, Yechezkel GH, Chenevix-Trench G, Offit K, Godwin AK, Struewing JP (2001) A single nucleotide polymorphism in the 5′ untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers. Cancer Epidemiol Biomark Prev 10:955–960

    CAS  Google Scholar 

  8. Hasselbach L, Haase S, Fischer D, Kolberg HC, Sturzbecher HW (2005) Characterisation of the promoter region of the human DNA-repair gene Rad51. Eur J Gynaecol Oncol 26:589–598

    CAS  PubMed  Google Scholar 

  9. Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BA, Pharoah PD, Dunning A (2002) Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet 11:1399–1407

    Article  CAS  PubMed  Google Scholar 

  10. Dufloth RM, Costa S, Schmitt F, Zeferino LC (2005) DNA repair gene polymorphisms and susceptibility to familial breast cancer in a group of patients from Campinas, Brazil. Genet Mol Res 4:771–782

    CAS  PubMed  Google Scholar 

  11. Lee KM, Choi JY, Kang C, Kang CP, Park SK, Cho H, Cho DY, Yoo KY, Noh DY, Ahn SH, Park CG, Wei Q, Kang D (2005) Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk. Clin Cancer Res 11:4620–4626

    Article  CAS  PubMed  Google Scholar 

  12. Webb PM, Hopper JL, Newman B, Chen X, Kelemen L, Giles GG, Southey MC, Chenevix-Trench G, Spurdle AB (2005) Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer. Cancer Epidemiol Biomark Prev 14:319–323

    Article  CAS  Google Scholar 

  13. Romanowicz-Makowska H, Smolarz B, Zadrozny M, Kulig A (2006) Analysis of RAD51 polymorphism and BRCA1 mutations in Polish women with breast cancer. Exp Oncol 28:156–159

    CAS  PubMed  Google Scholar 

  14. Brooks J, Shore RE, Zeleniuch-Jacquotte A, Currie D, Afanasyeva Y, Koenig KL, Arslan AA, Toniolo P, Wirgin I (2008) Polymorphisms in RAD51, XRCC2, and XRCC3 are not related to breast cancer risk. Cancer Epidemiol Biomark Prev 17:1016–1019

    Article  CAS  Google Scholar 

  15. Krupa R, Synowiec E, Pawlowska E, Morawiec Z, Sobczuk A, Zadrozny M, Wozniak K, Blasiak J (2009) Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Exp Mol Pathol 87:32–35

    Article  CAS  PubMed  Google Scholar 

  16. Jara L, Dubois K, Gaete D, de Mayo T, Ratkevicius N, Bravo T, Margarit S, Blanco R, Gomez F, Waugh E, Peralta O, Reyes JM, Ibanez G, Gonzalez-Hormazabal P (2010) Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population. Breast Cancer Res Treat

  17. Antoniou AC, Sinilnikova OM, Simard J, Leone M, Dumont M, Neuhausen SL, Struewing JP, Stoppa-Lyonnet D, Barjhoux L, Hughes DJ, Coupier I, Belotti M, Lasset C, Bonadona V, Bignon YJ, Rebbeck TR, Wagner T, Lynch HT, Domchek SM, Nathanson KL, Garber JE, Weitzel J, Narod SA, Tomlinson G, Olopade OI, Godwin A, Isaacs C, Jakubowska A, Lubinski J, Gronwald J, Gorski B, Byrski T, Huzarski T, Peock S, Cook M, Baynes C, Murray A, Rogers M, Daly PA, Dorkins H, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Niederacher D, Deissler H, Spurdle AB, Chen X, Waddell N, Cloonan N, Kirchhoff T, Offit K, Friedman E, Kaufmann B, Laitman Y, Galore G, Rennert G, Lejbkowicz F, Raskin L, Andrulis IL, Ilyushik E, Ozcelik H, Devilee P, Vreeswijk MP, Greene MH, Prindiville SA, Osorio A, Benitez J, Zikan M, Szabo CI, Kilpivaara O, Nevanlinna H, Hamann U, Durocher F, Arason A, Couch FJ, Easton DF, Chenevix-Trench G (2007) RAD51 135G–>C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 81:1186–1200

    Google Scholar 

  18. Blasiak J, Przybylowska K, Czechowska A, Zadrozny M, Pertynski T, Rykala J, Kolacinska A, Morawiec Z, Drzewoski J (2003) Analysis of the G/C polymorphism in the 5′-untranslated region of the RAD51 gene in breast cancer. Acta Biochim Pol 50:249–253

    CAS  PubMed  Google Scholar 

  19. Sliwinski T, Krupa R, Majsterek I, Rykala J, Kolacinska A, Morawiec Z, Drzewoski J, Zadrozny M, Blasiak J (2005) Polymorphisms of the BRCA2 and RAD51 genes in breast cancer. Breast Cancer Res Treat 94:105–109

    Article  CAS  PubMed  Google Scholar 

  20. Wang Z, Fu Y, Tang C, Lu S, Chu WM (2009) SULT1A1 R213H polymorphism and breast cancer risk: a meta-analysis based on 8,454 cases and 11,800 controls. Breast Cancer Res Treat

  21. Wang Z, Cui D, Lu W NBS1 8360G > C polymorphism is associated with breast cancer risk: a meta-analysis. (2010) Breast Cancer Res Treat

  22. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826

    CAS  PubMed  Google Scholar 

  23. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    CAS  PubMed  Google Scholar 

  24. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  25. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    CAS  PubMed  Google Scholar 

  26. Thompson LH, Schild D (2001) Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutat Res 477:131–153

    CAS  PubMed  Google Scholar 

  27. Rodrigue A, Lafrance M, Gauthier MC, McDonald D, Hendzel M, West SC, Jasin M, Masson JY (2006) Interplay between human DNA repair proteins at a unique double-strand break in vivo. EMBO J 25:222–231

    Article  CAS  PubMed  Google Scholar 

  28. Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, Edler L, Lubinski J, Scott RJ, Hamann U (2007) The RAD51 135 G>C polymorphism modifies breast cancer and ovarian cancer risk in Polish BRCA1 mutation carriers. Cancer Epidemiol Biomark Prev 16:270–275

    Article  CAS  Google Scholar 

  29. Gray NK (1998) Translational control by repressor proteins binding to the 5′UTR of mRNAs. Methods Mol Biol 77:379–397

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, 210029, China

    Zhanwei Wang

  2. Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Hairong Dong

  3. Dental Research Institute, School of Stomatology, Nanjing Medical University, Nanjing, 210029, China

    Yuanyuan Fu

  4. Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Haixia Ding

Authors
  1. Zhanwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hairong Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuanyuan Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haixia Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haixia Ding.

Additional information

Z. Wang and H. Dong contributed equally to this work and should be considered as co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Z., Dong, H., Fu, Y. et al. RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects. Breast Cancer Res Treat 124, 765–769 (2010). https://doi.org/10.1007/s10549-010-0885-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-010-0885-0

Keywords

Search

Navigation