Skip to main content

Advertisement

SpringerLink
Log in

XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis

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

Abstract

XRCC3 (X-ray repair complementing defective repair in Chinese hamster cells 3) is a member of the RecA/Rad51-related protein family that participates in homologous recombination, maintaining chromosome stability and participating in DNA repair. Attention has been drawn upon the association of XRCC3 Thr241Met polymorphism with breast cancer risk. The present meta-analysis aims to examine whether XRCC3 Thr241Met polymorphism status is associated with breast cancer risk. Apart from the overall meta-analysis, separate analyses were performed on Chinese and non-Chinese populations, in order to investigate race-specific effects. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to August 2009. Twenty case–control studies on non-Chinese subjects (19,575 cases and 21,125 controls) and three case–control studies on Chinese subjects (1,216 cases and 1,112 controls) were eligible. Pooled odds ratios (OR) were appropriately derived from fixed-effects or random-effects models. At the overall analysis, the T allele was associated with elevated breast cancer risk mainly following a recessive model (pooled OR = 1.064, 95% CI: 1.007–1.124, fixed effects), given that the effect was more pronounced in homozygous carriers (pooled OR = 1.073, 95% CI: 1.010–1.140, fixed effects). The association seemed confined in non-Chinese populations, once again following a recessive model (pooled OR = 1.072, 95% CI: 1.014–1.133, fixed effects). Concerning Chinese populations, no consistent results were demonstrated. In conclusion, the XRCC3 Thr241Met T allele seems associated with elevated breast cancer risk in non-Chinese subjects. The need for additional studies on Chinese populations seems warranted.

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
Fig. 3

Similar content being viewed by others

References

  1. Brenneman MA, Weiss AE, Nickoloff JA, Chen DJ (2000) XRCC3 is required for efficient repair of chromosome breaks by homologous recombination. Mutat Res 459:89–97

    CAS  PubMed  Google Scholar 

  2. Breast Cancer Association Consortium (2006) Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst 98:1382–1396

    Article  Google Scholar 

  3. Lee SA, Lee KM, Park SK, Choi JY, Kim B, Nam J, Yoo KY, Noh DY, Ahn SH, Kang D (2007) Genetic polymorphism of XRCC3 Thr241Met and breast cancer risk: case–control study in Korean women and meta-analysis of 12 studies. Breast Cancer Res Treat 103:71–76

    Article  CAS  PubMed  Google Scholar 

  4. Manuguerra M, Saletta F, Karagas MR, Berwick M, Veglia F, Vineis P, Matullo G (2006) XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review. Am J Epidemiol 164:297–302

    Article  PubMed  Google Scholar 

  5. Han J, Hankinson SE, Ranu H, De Vivo I, Hunter DJ (2004) Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses’ Health Study. Carcinogenesis 25:189–195

    Article  CAS  PubMed  Google Scholar 

  6. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  Google Scholar 

  7. 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 

  8. Smith TR, Levine EA, Perrier ND, Miller MS, Freimanis RI, Lohman K, Case LD, Xu J, Mohrenweiser HW, Hu JJ (2003) DNA-repair genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev 12:1200–1204

    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 et al (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. Kang D (2003) Genetic polymorphisms and cancer susceptibility of breast cancer in Korean women. J Biochem Mol Biol 36:28–34

    CAS  PubMed  Google Scholar 

  11. Han J, Hankinson SE, Zhang SM, De Vivo I, Hunter DJ (2004) Interaction between genetic variations in DNA repair genes and plasma folate on breast cancer risk. Cancer Epidemiol Biomarkers Prev 13:520–524

    Article  CAS  PubMed  Google Scholar 

  12. Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, Liu-Mares W, Hu JJ (2008) Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis 29:2132–2138

    Article  CAS  PubMed  Google Scholar 

  13. Bewick MA, Conlon MS, Lafrenie RM (2006) Polymorphisms in XRCC1, XRCC3, and CCND1 and survival after treatment for metastatic breast cancer. J Clin Oncol 24:5645–5651

    Article  CAS  PubMed  Google Scholar 

  14. Han S, Zhang HT, Wang Z, Xie Y, Tang R, Mao Y, Li Y (2006) DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies. Eur J Hum Genet 14:1136–1144

    Article  CAS  PubMed  Google Scholar 

  15. Goode EL, Ulrich CM, Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11:1513–1530

    CAS  PubMed  Google Scholar 

  16. Andreassen CN, Alsner J, Overgaard J, Herskind C, Haviland J, Owen R, Homewood J, Bliss J, Yarnold J (2005) TGFB1 polymorphisms are associated with risk of late normal tissue complications in the breast after radiotherapy for early breast cancer. Radiother Oncol 75:18–21

    Article  CAS  PubMed  Google Scholar 

  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 648:65–72

    CAS  PubMed  Google Scholar 

  18. Han J, Haiman C, Niu T, Guo Q, Cox DG, Willett WC, Hankinson SE, Hunter DJ (2009) Genetic variation in DNA repair pathway genes and premenopausal breast cancer risk. Breast Cancer Res Treat 115:613–622

    Article  CAS  PubMed  Google Scholar 

  19. Jacobsen NR, Nexo BA, Olsen A, Overvad K, Wallin H, Tjonneland A, Vogel U (2003) No association between the DNA repair gene XRCC3 T241M polymorphism and risk of skin cancer and breast cancer. Cancer Epidemiol Biomarkers Prev 12:584–585

    CAS  PubMed  Google Scholar 

  20. Smith TR, Miller MS, Lohman K, Lange EM, Case LD, Mohrenweiser HW, Hu JJ (2003) Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett 190:183–190

    Article  CAS  PubMed  Google Scholar 

  21. Figueiredo JC, Knight JA, Briollais L, Andrulis IL, Ozcelik H (2004) Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 13:583–591

    CAS  PubMed  Google Scholar 

  22. Forsti A, Angelini S, Festa F, Sanyal S, Zhang Z, Grzybowska E, Pamula J, Pekala W, Zientek H, Hemminki K et al (2004) Single nucleotide polymorphisms in breast cancer. Oncol Rep 11:917–922

    PubMed  Google Scholar 

  23. 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 

  24. Zhang L, Zhang Z, Yan W (2005) Single nucleotide polymorphisms for DNA repair genes in breast cancer patients. Clin Chim Acta 359:150–155

    Article  CAS  PubMed  Google Scholar 

  25. Millikan RC, Player JS, Decotret AR, Tse CK, Keku T (2005) Polymorphisms in DNA repair genes, medical exposure to ionizing radiation, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14:2326–2334

    Article  CAS  PubMed  Google Scholar 

  26. 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 Biomarkers Prev 14:319–323

    Article  CAS  PubMed  Google Scholar 

  27. Garcia-Closas M, Egan KM, Newcomb PA, Brinton LA, Titus-Ernstoff L, Chanock S, Welch R, Lissowska J, Peplonska B, Szeszenia-Dabrowska N et al (2006) Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses. Hum Genet 119:376–388

    Article  CAS  PubMed  Google Scholar 

  28. Thyagarajan B, Anderson KE, Folsom AR, Jacobs DR Jr, Lynch CF, Bargaje A, Khaliq W, Gross MD (2006) No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women’s Health Study. Cancer Detect Prev 30:313–321

    Article  CAS  PubMed  Google Scholar 

  29. Sangrajrang S, Schmezer P, Burkholder I, Boffetta P, Brennan P, Woelfelschneider A, Bartsch H, Wiangnon S, Cheisilpa A, Popanda O (2007) The XRCC3 Thr241Met polymorphism and breast cancer risk: a case-control study in a Thai population. Biomarkers 12:523–532

    Article  CAS  PubMed  Google Scholar 

  30. Costa S, Pinto D, Pereira D, Rodrigues H, Cameselle-Teijeiro J, Medeiros R, Schmitt F (2007) DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population. Breast Cancer Res Treat 103:209–217

    Article  CAS  PubMed  Google Scholar 

  31. 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 Biomarkers Prev 17:1016–1019

    Article  CAS  PubMed  Google Scholar 

  32. Loizidou MA, Michael T, Neuhausen SL, Newbold RF, Marcou Y, Kakouri E, Daniel M, Papadopoulos P, Malas S, Kyriacou K et al (2008) Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast Cancer Res Treat 112:575–579

    Article  CAS  PubMed  Google Scholar 

  33. 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 

  34. Au WW, Salama SA, Sierra-Torres CH (2003) Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 111:1843–1850

    CAS  PubMed  Google Scholar 

  35. Araujo FD, Pierce AJ, Stark JM, Jasin M (2002) Variant XRCC3 implicated in cancer is functional in homology-directed repair of double-strand breaks. Oncogene 21:4176–4180

    Article  CAS  PubMed  Google Scholar 

  36. Higgins JPT, Green S (eds) (2008) Cochrane handbook for systematic reviews of interventions version 5.0.1. The Cochrane collaboration, 2008. Available at www.cochrane-handbook.org. Accessed 29 Aug 2009

Download references

Author information

Authors and Affiliations

  1. School of Medicine, National University of Athens, Athens, Greece

    Konstantinos P. Economopoulos & Theodoros N. Sergentanis

  2. Society of Junior Doctors, 5 Menalou street, Maroussi, 15123, Athens, Greece

    Konstantinos P. Economopoulos & Theodoros N. Sergentanis

Authors
  1. Konstantinos P. Economopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theodoros N. Sergentanis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Konstantinos P. Economopoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Economopoulos, K.P., Sergentanis, T.N. XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 121, 439–443 (2010). https://doi.org/10.1007/s10549-009-0562-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-009-0562-3

Keywords

Search

Navigation