Breast Cancer Research and Treatment

, Volume 95, Issue 2, pp 153–159 | Cite as

Microsatellite profile in hormonal receptor genes associated with breast cancer



Given that breast cancer is depending on multiple hormonal influences, the nuclear receptors, estrogen receptor alpha, estrogen receptor beta and androgen receptor, are candidates for cancer susceptibility markers. We conducted an association study in a case-control population (139 cases and 145 controls) by genotyping three potentially functional microsatellites (TA)n, (CA)n and (CAG)n in the ERa, ERb and AR genes respectively. For (CAG)n polymorphism, a significant difference was observed using a cut-off 15 repeats CAG between genotypes short-short/short-long/long-long in cases and control subjects (p=0.009) and also between the distribution of short/long allele in the two groups of individuals (p=0.001). Genotypes comprising one or two short (CAG)n sequences had higher risk of breast cancer compared to genotypes with two long allele (odds ratio=1,93; confidence interval=1.05–3.55; p=0.03). No significant difference was observed in allele frequency or in short/long allele percentage for (CA)n or (TA)n polymorphism (cut-off 22 CA and 19 TA repeats), neither in genotype frequencies (short-short, short-long or long-long). When the three microsatellite genotype were taken in analysis, the profile short CA-long TA-short CAG could clearly discriminate between cases and controls (p=0.006). Also, this combined genotype profile has greater predictive values for breast cancer than (CAG)n genotype alone (predictive positive value 57,1% versus 53,7% and predictive negative value 53% versus 23% respectively). Our results sustain a polygenic model of breast cancer with gene-gene interactions; combined effects of three low-risk polymorphisms conferred significant genetic predisposition. Genotyping hormonal receptor genes ERa, ERb and AR could be a useful genetic marker for defining disease risk.


allele length polymorphism breast cancer genetic profile hormonal receptor microsatellite tandem repeats 



androgen receptor


estrogen receptor alpha


estrogen receptor beta


single nucleotide polymorphism


short tandem repeat


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



We thank Prof. Seffert (Gynecology Department, University Hospital of St Etienne) who kindly contributed to the enrolment of patients in this study and Claire Siterre for the excellent technical help. The work was supplied by clinical research funds from St Etienne University Hospital.


  1. 1.
    Chen YC, Hunter DJ Molecular epidemiology of cancer CA Cancer J Clin 55 1: 45–54, 2005PubMedCrossRefGoogle Scholar
  2. 2.
    Dunning A, Healey CS, Pharoah PDP, Dawn Teare M, Ponder BAJ, Easton DF A systematic review of genetic polymorphisms and breast cancer risk Cancer Epidemiol Biomark Prev 8 10: 843–854, 1999Google Scholar
  3. 3.
    Hankinson SE, Willett WC, Manson JAE, Colditz GA, Hunter DJ, Spiegelman D, Barbieri RL, Speizer FE Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women J Natl Cancer Inst 90 17: 1292–1299, 1998PubMedCrossRefGoogle Scholar
  4. 4.
    Russo J, Russo IH Genotoxicity of steroidal estrogens Trends Endocrinol Metab 15 5: 211–218, 2004CrossRefPubMedGoogle Scholar
  5. 5.
    Leung G, Tsao SW, Wong YC The effect of flutamide and tamoxifen on sex hormone-induced mammary carcinogenesis and pituitary adenoma Breast Cancer Res Treat 72 2: 153–162, 2002CrossRefPubMedGoogle Scholar
  6. 6.
    Yeh S, Yueh-Chiang H, Wang PH, Xie C, Xu Q, Tsai MY, Dong Z, Wang RS, Lee TH, Chang C Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor J Exp Med 198 12:1899–1908, 2003CrossRefPubMedGoogle Scholar
  7. 7.
    Lanzino M, De Amicis F, McPhaul MJ, Marsico S, Panno ML, Ando S Endogenous coactivator ARA70 interacts with estrogen receptor alpha and modulates the functional ERalpha/androgen receptor interplay in MCF-7 cells J Biol Chem 280 21:20421–20430, 2005CrossRefPubMedGoogle Scholar
  8. 8.
    Maggiolini M, Donze O, Jeannin E, Ando S, Picard D Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor alpha Cancer Res 59 19: 4864–4869, 1999PubMedGoogle Scholar
  9. 9.
    Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS 1997 Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites Science 277(5331): 1508–1510CrossRefPubMedGoogle Scholar
  10. 10.
    Wedren S, Lovmar L, Humphreys K, Magnusson C, Melhus H, Syvanen C, Kindmark A, landegren U, Lagerstrom Fermer M, Stiger F, Persson I, Baron J, Weiderpass E Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study Breast Cancer Res 6 4: R437–R449, 2004CrossRefPubMedGoogle Scholar
  11. 11.
    Wang B, Ren J, Ooi LLPJ, Chong SS, Lee CGL Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients Oncogene 24 24:3999–4008, 2005CrossRefPubMedGoogle Scholar
  12. 12.
    Cai Q, Gao YT, Wen W, Shu XO, Jin F, Smith JR, Zheng W Association of breast cancer risk with a GT dinucleotide repeat polymorphism upstream of the estrogen receptor-alpha gene Cancer Res 63 18: 5727–5730, 2003PubMedGoogle Scholar
  13. 13.
    Forsti A, Zhao C, Israelsson E, Dahlman-Wright K, Gustafsson JA, Hemminki K, 2003 Polymorphisms in the estrogen receptor beta gene and risk of breast cancer: no association Breast Cancer Res Treat 79(3): 409–413CrossRefPubMedGoogle Scholar
  14. 14.
    Dunning AM, McBride S, Gregory J, Durocher F, Foster NA, Healey CS, Smith N, Pharoah PDP, Luben RN, Easton DF, Ponder BAJ No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer Carcinogenesis 20 11: 2131–2135, 1999CrossRefPubMedGoogle Scholar
  15. 15.
    Spurdle AB, Dite GS, Chen X, Mayne CJ, Southey MC, Batten LE, Chy H, Trute L, McCredie MRE, Giles GG, Armes J, Venter DJ, Hopper JL, Chenevix-Trench G Androgen receptor exon 1CAG repeat length and breast cancer in women before age forty years JNCI 91 11: 961–966, 1999CrossRefPubMedGoogle Scholar
  16. 16.
    Kadouri L, Easton DE, Edwards S, Hubert A, Kote-Jarai Z, Glaser B, Durocher F, Abeliovich D, Peretz T, Eales RA CAG and GGC repeat polymorphism in the androgen receptor gene and breast cancer susceptibility in BRCA1/2 carriers and non-carriers Br J Cancer 85 1: 36–40, 2001CrossRefPubMedGoogle Scholar
  17. 17.
    Menin C, Banna GL, De Salvo G, Lazzarotto V, De Nicolo A, Agata S, Montagna M, Sordi G, Nicoletto O, Chicco-Bianchi L D’Andrea E Lack of an association between androgen receptor CAG polymorphism and familial breast/ovarian cancer Cancer Lett 168 1: 31–36, 2001CrossRefPubMedGoogle Scholar
  18. 18.
    Haiman CA, Brown M, Hankinson SE, Spiegelman D, Colditz GA, Willett WC, Kantoff PW, Hunter DJ The androgen receptor CAG repeat polymorphism and risk of breats cancer in the Nurses’ Health Study Cancer Res 62 4: 1045–1049, 2002PubMedGoogle Scholar
  19. 19.
    Giguere Y, Dewailly E, Brisson J, Ayotte P, Laflamme N, Demers A, Forest VI, Dodin S, Robert J, Rousseau F Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population Cancer Res 61 15: 5869–5874, 2001PubMedGoogle Scholar
  20. 20.
    Yu H, Bharaj B, Vassilikos EJK, Giai M, Diamandis EP 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, 2000CrossRefPubMedGoogle Scholar
  21. 21.
    Rebbeck TR, Kantoff PW, Krithivas K, Neuhausen S, Blackwood MA, Godwin AK, Daly MB, Narod SA, Garber JE, Lynch HT, Weber BL, Brown M Modification of BRCA1 associated breast cancer risk by the polymorphic androgen-receptor CAG repeat Am J Hum Genet 64 5: 1371–1377, 1999CrossRefPubMedGoogle Scholar
  22. 22.
    Westberg L, Baghaei F, Rosmond R, Hellstrand M, Landen M, Jansson M, Holm G, Bjorntorp P, Eriksson E Polymorphism of the androgen receptor gene and the estrogen receptor b gene are associated with androgen levels in women J Clin Endocrinol Metab 86 6: 2562–2568, 2001CrossRefPubMedGoogle Scholar
  23. 23.
    Sharma VK, Brahmachari SK, Ramachandran S 3(TG/CA)n repeats in human gene families: abundance and selective patterns of distribution according to function and gene length BMC Genomics 6 1: 83–95, 2005CrossRefPubMedGoogle Scholar
  24. 24.
    Kato S, Endoh Y, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase Science 270 5241: 1491–1494, 1995PubMedCrossRefGoogle Scholar
  25. 25.
    Chamberlain NL, Driver ED, Miesfeld RL The length and location of CAG trinucletide repeats in the androgen receptor N-terminal domain affect transactivation function Nucleic Acids Res 22 15: 3181–3186, 1994PubMedCrossRefGoogle Scholar
  26. 26.
    Schadt EE, Monks SA, Drake TA, Lusis AJ, Che N, Colinayo V, Ruff TG, Milligan SB, lamb JR, Cavet G, Linsley PS, Mao M, Stoughton RB, Friend SH Genetics in gene expression surveyed in maize, mouse and man. Nature 422 6929: 297–302, 2003CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Immunology LaboratoryUniversity Hospital of St EtienneSt. Etienne Cedex 2France
  2. 2.Trefilerie Informatics CenterUniversity of St EtienneSt. EtienneFrance

Personalised recommendations