Advertisement

Breast Cancer Research and Treatment

, Volume 126, Issue 2, pp 365–371 | Cite as

RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers: evidence from a meta-analysis of 12 studies

  • Ke-Da Yu
  • Chen Yang
  • Lei Fan
  • Ao-Xiang Chen
  • Zhi-Ming Shao
Preclinical study

Abstract

A single-nucleotide polymorphism (SNP) in the 5′-untranslated region (UTR) of RAD51, 135G>C (rs1801320), was reported to be associated with an increased risk of breast cancer among BRCA2 as well as BRCA1 carriers. A few studies have also investigated the genetic contribution of RAD51 135G>C to the risk of sporadic breast cancers or breast cancer in non-BRCA1/2 carriers, though the results are yet controversial and inconclusive. We, in this study, performed a more precise estimation of the relationship between 135G>C and breast cancer among non-BRCA1/2 mutation carriers by meta-analyzing the currently available evidence from the literature. A total of 12 studies involving 7,065 cases and 6,981 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, there was no evidence for a significant association between 135G>C and breast cancer risk in non-BRCA1/2 mutation carriers (for CC vs. GG: OR = 0.995, 95%CI: 0.741–1.336; for GC vs. GG: OR = 0.959, 95%CI: 0.869–1.057; for dominant model: OR = 0.988, 95%CI: 0.902–1.082; and for recessive model: OR = 1.037, 95%CI: 0.782–1.376). We also performed subgroup analysis by ethnicity (Caucasian) as well as did analysis using the studies fulfilling Hardy–Weinberg equilibrium, and the results did not change. In summary, the present meta-analysis suggests that the RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers.

Keywords

RAD51 rs1801320 Breast cancer Susceptibility Meta-analysis 

Notes

Acknowledgments

This research is supported by grants from the National Basic Research Program of China (2006CB910501), 2009 Youth Foundation of Shanghai Public Health Bureau, 2009 Youth Foundation of Shanghai Medical College, and the National Natural Science Foundation of China (30971143, 30972936).

Conflict of interest statement

All authors declared no potential conflicts of interest.

References

  1. 1.
    Mohindra A, Hays LE, Phillips EN, Preston BD, Helleday T, Meuth M (2002) Defects in homologous recombination repair in mismatch-repair-deficient tumour cell lines. Hum Mol Genet 11:2189–2200PubMedCrossRefGoogle Scholar
  2. 2.
    Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM (1997) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88:265–275PubMedCrossRefGoogle Scholar
  3. 3.
    Scully R, Xie A, Nagaraju G (2004) Molecular functions of BRCA1 in the DNA damage response. Cancer Biol Ther 3:521–527PubMedGoogle Scholar
  4. 4.
    Ralhan R, Kaur J, Kreienberg R, Wiesmuller L (2007) Links between DNA double strand break repair and breast cancer: accumulating evidence from both familial and nonfamilial cases. Cancer Lett 248:1–17PubMedCrossRefGoogle Scholar
  5. 5.
    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 98:3232–3236PubMedCrossRefGoogle Scholar
  6. 6.
    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 Biomarkers Prev 10:955–960PubMedGoogle Scholar
  7. 7.
    Kadouri L, Kote-Jarai Z, Hubert A, Durocher F, Abeliovich D, Glaser B, Hamburger T, Eeles RA, Peretz T (2004) A single-nucleotide polymorphism in the RAD51 gene modifies breast cancer risk in BRCA2 carriers, but not in BRCA1 carriers or noncarriers. Br J Cancer 90:2002–2005PubMedCrossRefGoogle Scholar
  8. 8.
    Jakubowska A, Narod SA, Goldgar DE, Mierzejewski M, Masojc B, Nej K, Huzarska J, Byrski T, Gorski B, Lubinski J (2003) Breast cancer risk reduction associated with the RAD51 polymorphism among carriers of the BRCA1 5382insC mutation in Poland. Cancer Epidemiol Biomarkers Prev 12:457–459PubMedGoogle Scholar
  9. 9.
    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 81:1186–1200PubMedCrossRefGoogle Scholar
  10. 10.
    Yu KD, Chen AX, Yang C, Qiu LX, Fan L, Xu WH and Shao ZM (2009) Current evidence on the relationship between polymorphisms in the COX-2 gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat (in press) doi: 10.1007/s10549-10009-10688-10543
  11. 11.
    Yu KD, Di GH, Fan L, Chen AX, Yang C and Shao ZM (2009) Lack of an association between a functional polymorphism in the interleukin-6 gene promoter and breast cancer risk: a meta-analysis involving 25,703 subjects. Breast Cancer Res Treat (in press) doi: 10.1007/s10549-10009-10706-10545
  12. 12.
    Yu KD, Di GH, Fan L, Wu J, Hu Z, Shen ZZ, Huang W, Shao ZM (2009) A functional polymorphism in the promoter region of GSTM1 implies a complex role for GSTM1 in breast cancer. Faseb J 23:2274–2287PubMedCrossRefGoogle Scholar
  13. 13.
    Yu KD, Di GH, Fan L, Shao ZM (2009) Test of Hardy-Weinberg equilibrium in breast cancer case-control studies: an issue may influence the conclusions. Breast Cancer Res Treat 117:675–677PubMedCrossRefGoogle Scholar
  14. 14.
    Wittke-Thompson JK, Pluzhnikov A, Cox NJ (2005) Rational inferences about departures from Hardy-Weinberg equilibrium. Am J Hum Genet 76:967–986PubMedCrossRefGoogle Scholar
  15. 15.
    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 11:1399–1407PubMedCrossRefGoogle Scholar
  16. 16.
    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 50:249–253PubMedGoogle Scholar
  17. 17.
    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 4:771–782PubMedGoogle Scholar
  18. 18.
    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 11:4620–4626PubMedCrossRefGoogle Scholar
  19. 19.
    Romanowicz-Makowska H, Smolarz B, Kulig A (2005) Germline BRCA1 mutations and G/C polymorphism in the 5′-untranslated region of the RAD51 gene in Polish women with breast cancer. Pol J Pathol 56:161–165PubMedGoogle Scholar
  20. 20.
    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 94:105–109PubMedCrossRefGoogle Scholar
  21. 21.
    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 14:319–323PubMedCrossRefGoogle Scholar
  22. 22.
    Chang TW, Wang SM, Guo YL, Tsai PC, Huang CJ, Huang W (2006) Glutathione S-transferase polymorphisms associated with risk of breast cancer in southern Taiwan. Breast 15:754–761PubMedCrossRefGoogle Scholar
  23. 23.
    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 28:156–159PubMedGoogle Scholar
  24. 24.
    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 17:1016–1019PubMedCrossRefGoogle Scholar
  25. 25.
    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 103:209–217PubMedCrossRefGoogle Scholar
  26. 26.
    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 Biomarkers Prev 16:270–275PubMedCrossRefGoogle Scholar
  27. 27.
    Jara L, Acevedo ML, Blanco R, Castro VG, Bravo T, Gomez F, Waugh E, Peralta O, Cabrera E, Reyes JM, Ampuero S, Gonzalez-Hormazabal P (2007) RAD51 135G>C polymorphism and risk of familial breast cancer in a South American population. Cancer Genet Cytogenet 178:65–69PubMedCrossRefGoogle Scholar
  28. 28.
    Pharoah PD, Tyrer J, Dunning AM, Easton DF, Ponder BA (2007) Association between common variation in 120 candidate genes and breast cancer risk. PLoS Genet 3:e42PubMedCrossRefGoogle Scholar
  29. 29.
    Pooley KA, Baynes C, Driver KE, Tyrer J, Azzato EM, Pharoah PD, Easton DF, Ponder BA, Dunning AM (2008) Common single-nucleotide polymorphisms in DNA double-strand break repair genes and breast cancer risk. Cancer Epidemiol Biomarkers Prev 17:3482–3489PubMedCrossRefGoogle Scholar
  30. 30.
    Jakubowska A, Jaworska K, Cybulski C, Janicka A, Szymanska-Pasternak J, Lener M, Narod SA, Lubinski J (2009) Do BRCA1 modifiers also affect the risk of breast cancer in non-carriers? Eur J Cancer 45:837–842PubMedCrossRefGoogle Scholar
  31. 31.
    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 87:32–35PubMedCrossRefGoogle Scholar
  32. 32.
    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 648:65–72PubMedCrossRefGoogle Scholar
  33. 33.
    Palanca Suela S, Esteban Cardenosa E, Barragan Gonzalez E, de Juan Jimenez I, Chirivella Gonzalez I, Segura Huerta A, Guillen Ponce C, Martinez de Duenas E, Montalar Salcedo J, Castel Sanchez V, Bolufer Gilabert P (2010) CASP8 D302H polymorphism delays the age of onset of breast cancer in BRCA1 and BRCA2 carriers. Breast Cancer Res Treat 119:87–93PubMedCrossRefGoogle Scholar
  34. 34.
    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 (in press) doi  10.1007/s10549-10009-10709-10542
  35. 35.
    Shivji MK, Davies OR, Savill JM, Bates DL, Pellegrini L, Venkitaraman AR (2006) A region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchange. Nucleic Acids Res 34:4000–4011PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Ke-Da Yu
    • 1
    • 2
  • Chen Yang
    • 1
    • 2
  • Lei Fan
    • 1
    • 2
  • Ao-Xiang Chen
    • 1
    • 2
  • Zhi-Ming Shao
    • 1
    • 2
    • 3
  1. 1.Department of Breast Surgery, Cancer Center/Cancer InstituteFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiPeople’s Republic of China
  3. 3.Institutes of Biomedical ScienceFudan UniversityShanghaiPeople’s Republic of China

Personalised recommendations