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Association between androgen receptor gene CAG repeat polymorphism and breast cancer risk: a meta-analysis

  • Epidemiology
  • Published:
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Abstract

Androgens have been hypothesized to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol and their binding to the estrogen receptor and/or androgen receptor (AR) in the breast. The CAG repeat polymorphism in AR exon 1 has been implicated in breast cancer risk; however, studies on the association between this polymorphism and breast cancer risk remain conflicting. In order to derive a more precise estimation of the relationship, a large population-based case–control study was performed. We found that a long CAG sequence has a protective effect on breast cancer using an a priori determined cutoff (<22 or ≥22) in a dominant model analysis [SL–LL vs. SS, odds ratio (OR) = 0.86, 95% confidence intervals (CI): 0.67–1.10]. A similar result was obtained by analyzing seven detailed genotyping case–control studies by allele comparison in dominant and recessive models. However, larger scale primary study is required to further evaluate the interaction of AR CAG polymorphism and breast cancer risk.

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References

  1. Chamberlain NL, Driver ED, Miesfeld RL (1994) The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucl Acids Res 22(15):3181–3186

    Article  CAS  PubMed  Google Scholar 

  2. Kazemi-Esfarjani P, Trifiro MA, Pinsky L (1995) Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: possible pathogenetic relevance for the (CAG)n-expanded neuronopathies. Hum Mol Genet 4(4):523–527

    Article  CAS  PubMed  Google Scholar 

  3. Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Dahl D, Brufsky A, Talcott J, Hennekens CH, Kantoff PW (1997) The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci USA 94(7):3320–3323

    Article  CAS  PubMed  Google Scholar 

  4. Giguere Y, Dewailly E, Brisson J, Ayotte P, Laflamme N, Demers A, Forest VI, Dodin S, Robert J, Rousseau F (2001) Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population. Cancer Res 61(15):5869–5874

    CAS  PubMed  Google Scholar 

  5. Rebbeck TR, Kantoff PW, Krithivas K, Neuhausen S, Blackwood MA, Godwin AK, Daly MB, Narod SA, Garber JE, Lynch HT et al (1999) Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat. Am J Hum Genet 64(5):1371–1377

    Article  CAS  PubMed  Google Scholar 

  6. Dagan E, Friedman E, Paperna T, Carmi N, Gershoni-Baruch R (2002) Androgen receptor CAG repeat length in Jewish Israeli women who are BRCA1/2 mutation carriers: association with breast/ovarian cancer phenotype. Eur J Hum Genet 10(11):724–728

    Article  CAS  PubMed  Google Scholar 

  7. Spurdle AB, Dite GS, Chen X, Mayne CJ, Southey MC, Batten LE, Chy H, Trute L, McCredie MR, Giles GG et al (1999) Androgen receptor exon 1 CAG repeat length and breast cancer in women before age forty years. J Natl Cancer Inst 91(11):961–966

    Article  CAS  PubMed  Google Scholar 

  8. Spurdle AB, Antoniou AC, Duffy DL, Pandeya N, Kelemen L, Chen X, Peock S, Cook MR, Smith PL, Purdie DM et al (2005) The androgen receptor CAG repeat polymorphism and modification of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 7(2):R176–R183

    Article  CAS  PubMed  Google Scholar 

  9. Dunning AM, McBride S, Gregory J, Durocher F, Foster NA, Healey CS, Smith N, Pharoah PD, Luben RN, Easton DF et al (1999) No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer. Carcinogenesis 20(11):2131–2135

    Article  CAS  PubMed  Google Scholar 

  10. Kadouri L, Easton DF, Edwards S, Hubert A, Kote-Jarai Z, Glaser B, Durocher F, Abeliovich D, Peretz T, Eeles RA (2001) CAG and GGC repeat polymorphisms in the androgen receptor gene and breast cancer susceptibility in BRCA1/2 carriers and non-carriers. Br J Cancer 85(1):36–40

    Article  CAS  PubMed  Google Scholar 

  11. Given HF, Radbourne R, Oag H, Merritt S, Barclay E, Hanby AM, Lamlum H, McGrath J, Curran C, Tomlinson IP (2000) The androgen receptor exon 1 trinucleotide repeat does not act as a modifier of the age of presentation in breast cancer. Eur J Cancer 36(4):533–534

    Article  CAS  PubMed  Google Scholar 

  12. Yu H, Bharaj B, Vassilikos EJ, Giai M, Diamandis EP (2000) Shorter CAG repeat length in the androgen receptor gene is associated with more aggressive forms of breast cancer. Breast Cancer Res Treat 59(2):153–161

    Article  CAS  PubMed  Google Scholar 

  13. Iobagiu C, Lambert C, Normand M, Genin C (2006) Microsatellite profile in hormonal receptor genes associated with breast cancer. Breast Cancer Res Treat 95(2):153–159

    Article  CAS  PubMed  Google Scholar 

  14. De Abreu FB, Pirolo LJ, Canevari Rde A, Rosa FE, Moraes Neto FA, Caldeira JR, Rainho CA, Rogatto SR (2007) Shorter CAG repeat in the AR gene is associated with atypical hyperplasia and breast carcinoma. Anticancer Res 27(2):1199–1205

    PubMed  Google Scholar 

  15. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127(9):820–826

    CAS  PubMed  Google Scholar 

  16. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  17. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    CAS  PubMed  Google Scholar 

  18. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    CAS  PubMed  Google Scholar 

  19. Zhang W, Yu YY (2007) Polymorphisms of short tandem repeat of genes and breast cancer susceptibility. Eur J Surg Oncol 33(5):529–534

    Article  CAS  PubMed  Google Scholar 

  20. Suter NM, Malone KE, Daling JR, Doody DR, Ostrander EA (2003) Androgen receptor (CAG)n and (GGC)n polymorphisms and breast cancer risk in a population-based case-control study of young women. Cancer Epidemiol Biomarkers Prev 12(2):127–135

    CAS  PubMed  Google Scholar 

  21. Cox DG, Blanche H, Pearce CL, Calle EE, Colditz GA, Pike MC, Albanes D, Allen NE, Amiano P, Berglund G et al (2006) A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). Breast Cancer Res 8(5):R54

    Article  PubMed  Google Scholar 

  22. Maggiolini M, Donze O, Jeannin E, Ando S, Picard D (1999) Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor alpha. Cancer Res 59(19):4864–4869

    CAS  PubMed  Google Scholar 

  23. Wooster R, Mangion J, Eeles R, Smith S, Dowsett M, Averill D, Barrett-Lee P, Easton DF, Ponder BA, Stratton MR (1992) A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. Nat Genet 2(2):132–134

    Article  CAS  PubMed  Google Scholar 

  24. Zhu X, Daffada AA, Chan CM, Dowsett M (1997) Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer. Int J Cancer 72(4):574–580

    Article  CAS  PubMed  Google Scholar 

  25. Tsezou A, Tzetis M, Gennatas C, Giannatou E, Pampanos A, Malamis G, Kanavakis E, Kitsiou S (2008) Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer. Breast 17(2):159–166

    Article  CAS  PubMed  Google Scholar 

  26. Haiman CA, Brown M, Hankinson SE, Spiegelman D, Colditz GA, Willett WC, Kantoff PW, Hunter DJ (2002) The androgen receptor CAG repeat polymorphism and risk of breast cancer in the Nurses’ Health Study. Cancer Res 62(4):1045–1049

    CAS  PubMed  Google Scholar 

  27. Liede A, Zhang W, De Leon Matsuda ML, Tan A, Narod SA (2003) Androgen receptor gene polymorphism and breast cancer susceptibility in The Philippines. Cancer Epidemiol Biomarkers Prev 12(9):848–852

    CAS  PubMed  Google Scholar 

  28. Wang W, John EM, Ingles SA (2005) Androgen receptor and prostate-specific antigen gene polymorphisms and breast cancer in African-American women. Cancer Epidemiol Biomarkers Prev 14(12):2990–2994

    Article  CAS  PubMed  Google Scholar 

  29. Wedren S, Magnusson C, Humphreys K, Melhus H, Kindmark A, Stiger F, Branting M, Persson I, Baron J, Weiderpass E (2007) Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 16(9):1775–1783

    Article  CAS  PubMed  Google Scholar 

  30. Gonzalez A, Javier Dorta F, Rodriguez G, Brito B, Rodriguez MA, Cabrera A, Diaz-Chico JC, Reyes R, Aguirre-Jaime A, Nicolas Diaz-Chico B (2007) Increased risk of breast cancer in women bearing a combination of large CAG and GGN repeats in the exon 1 of the androgen receptor gene. Eur J Cancer 43(16):2373–2380

    Article  CAS  PubMed  Google Scholar 

  31. Slattery ML, Sweeney C, Murtaugh M, Ma KN, Caan BJ, Potter JD, Wolff R (2006) Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer. Int J Cancer 118(12):3140–3146

    Article  CAS  PubMed  Google Scholar 

  32. Wu MH, Chou YC, Yu CP, Yang T, You SL, Chen CJ, Sun CA (2008) Androgen receptor gene CAG repeats, estrogen exposure status, and breast cancer susceptibility. Eur J Cancer Prev 17(4):317–322

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

We thank Dr. Nora Tramm at the University of Chicago for English improvement and comments on the manuscript.

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Authors and Affiliations

  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People’s Republic of China

    YongSheng Huang

  2. James Frank Institute, The University of Chicago, Chicago, IL, 60637, USA

    YouJin Hao

  3. Laboratorio Nacional de Genómica para la Biodiversidad, CINVESTAV-IPN, Km 9.6 Libramiento Norte, Carretera Irapuato – León, CP 36821, Irapuato, Guanajuato, Mexico

    Rafael Montiel

  4. Ben May Department for Cancer Research, University of Chicago, 929 East 57th Street, W325, Chicago, IL, 60637, USA

    BingHui Li, Enyi Huang & Lewie Zeng

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  1. YouJin Hao
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  2. Rafael Montiel
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  3. BingHui Li
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Correspondence to YongSheng Huang.

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Hao, Y., Montiel, R., Li, B. et al. Association between androgen receptor gene CAG repeat polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 124, 815–820 (2010). https://doi.org/10.1007/s10549-010-0907-y

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  • DOI: https://doi.org/10.1007/s10549-010-0907-y

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