Advertisement

Tumor Biology

, Volume 37, Issue 6, pp 8067–8074 | Cite as

Association of estrogen and progesterone receptor gene polymorphisms and their respective hormones in uterine leiomyomas

  • M. Veronica
  • Altaf Ali
  • A. Venkateshwari
  • D. Mamata
  • Pratibha Nallari
Original Article

Abstract

The steroid hormones estradiol and progesterone play an important role in the pathophysiology of fibroids that occurs in 20–25 % of women in the reproductive age. Our study examines the risk imposed by estrogen and progesterone plasma levels in correlation with the ERβ (−13950T/C) and PGR (+331G/A) receptor gene polymorphisms. The study population included 296 individuals (146 UL cases and 150 female controls). Hormonal levels were estimated by ELISA and genotyping was carried out by PCR-RFLP analysis, and the obtained results were statistically analyzed. Estrogen levels were found to be high in cases with the “TC” genotype of ERβ receptor polymorphism compared to controls, whereas individuals with “GA” and “AA” genotype of PGR receptor polymorphism showed high progesterone levels for cases when compared to controls. The TC genotype of the ERβ receptor polymorphism and the GA and AA genotypes of the PGR receptor polymorphism and their respective hormonal levels can be developed as markers in the prediction of uterine fibroids.

Keywords

Estrogen Progesterone Uterine leiomyomas Reproduction Infertility 

Notes

Acknowledgments

Financial assistance from University Grants Commission, New Delhi and Maulana Azad National Fellowship, University Grants Commission, New Delhi, is sincerely acknowledged.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2015_4711_MOESM1_ESM.doc (30 kb)
Supplementary Table 1 (DOC 29 kb)

References

  1. 1.
    Renner SP, Strick R, Fasching PA, Oeser S, Oppelt P, Mueller S, et al. Single nucleotide polymorphisms in the progesterone receptor gene and association with uterine leiomyoma tumor characteristics and disease risk. Am J Obstet Gynecol. 2008;199:648.e1–9.CrossRefGoogle Scholar
  2. 2.
    Khan AT, Shehmar M, Gupta JK. Uterine fibroids: current perspectives. Int J Women’s Health. 2014;6:95–114.CrossRefGoogle Scholar
  3. 3.
    Falcone T, Walters MD. Hysterectomy for benign disease. Obstet Gynecol. 2008;111:753–67.CrossRefPubMedGoogle Scholar
  4. 4.
    Sosna O, Kolesar L, Slavčev A, Skibova J, Fait T, Mara M, et al. Th1/Th2 cytokine gene polymorphisms in patients with uterine fibroid. Folia Biol (Praha). 2010;56:206–10.Google Scholar
  5. 5.
    Fischer C, Juhasz-Boess I, Lattrich C, Ortmann O, Treeck O. Estrogen receptor β gene polymorphisms and susceptibility to uterine fibroids. Gynecol Endocrinol. 2010;26(1):4–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Villanova FE, Andrade PM, Otsuka AY, Gomes MTV, Leal ES, Castro RA, et al. Estrogen receptor alpha polymorphism and susceptibility to uterine leiomyoma. Steroids. 2006;7(1):960–5.CrossRefGoogle Scholar
  7. 7.
    Valladares F, Frías I, Báez D, García C, López FJ, Fraser JD, et al. Characterization of estrogen receptors alpha and beta in uterine leiomyoma cells. Fertil Steril. 2006;86(6):1736–43.CrossRefPubMedGoogle Scholar
  8. 8.
    Nierth-Simpson EN, Martin MM, Chiang TC, Melnik LI, Rhodes LV, Muir SE, et al. Human uterine smooth muscle and leiomyoma cells differ in their rapid 17β-estradiol signaling: implications for proliferation. Endocrinology. 2009;150(5):2436–45.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Ishikawa H, Ishi K, Serna VA, Kakazu R, Bulun SE, Kurita T. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology. 2010;151(6):2433–42.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Vivo ID, Hankinson SE, Colditz GA, Hunter DJ. A functional polymorphism in the progesterone receptor gene is associated with an increase in breast cancer risk. Cancer Res. 2003;63:5236–8.PubMedGoogle Scholar
  11. 11.
    Fabjani G, Tong D, Czerwenka K, Schuster E, Speiser P, Leodolter S, et al. Human progesterone receptor gene polymorphism PROGINS and risk for breast cancer in Austrian women. Breast Cancer Res Treat. 2002;72:131–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Chaudhary S, Panda AK, Mishra DR, Mishra KS. Association of +331G/A PgR polymorphism with susceptibility to female reproductive cancer: evidence from a meta-analysis. PLoS One. 2013;8(1), e53308.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lahiri DK, Nurnberger JI. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19(19):5444.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ali SM, Mahnaz S, Mahmood T. Rapid genomic DNA extraction (RGDE). Forensic Sci Int Genet Suppl Ser. 2008;1:63–5.CrossRefGoogle Scholar
  15. 15.
    Chen HY, Wan L, Chung YW, Chen WC, Tsai FJ, Tsai CH. Estrogen receptor beta gene haplotype is associated with pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol. 2008;138:105–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Ludwig AH, Murawska M, Panek G, Timorek A, Kupryjanczyk J. Androgen, progesterone, and FSH receptor polymorphisms in ovarian cancer risk and outcome. Endocr Relat Cancer. 2009;16:1005–16.CrossRefPubMedGoogle Scholar
  17. 17.
    Flake GP, Andersen J, Dixon D. Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect. 2003;111:1037–54.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ciavattini A, Giuseppe JD, Stortoni P, Montik N, Giannubilo SR, Litta P, et al. Uterine fibroids: pathogenesis and interactions with endometrium and endomyometrial junction. Obstet Gynecol Int. 2013;1–11.Google Scholar
  19. 19.
    Hsieh YY, Wang YK, Chang CC, Lin CS. Estrogen receptor α-351 XbaI*G and −397 PvuII*C-related genotypes and alleles are associated with higher susceptibilities of endometriosis and leiomyoma. Mol Hum Reprod. 2007;13(2):117–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Thellenberg-Karlsson C, Lindstrom S, Malmer B, Wiklund F, Augustsson-Balter K, Adami H-O, et al. Estrogen receptor β polymorphism is associated with prostate cancer risk. Clin Cancer Res. 2006;12(6):1936–41.CrossRefPubMedGoogle Scholar
  21. 21.
    Passarelli MN, Phipps AI, Potter JD, Makar KW, Coghill AE, Wernli KJ, et al. Common single-nucleotide polymorphisms in the estrogen receptor β promoter are associated with colorectal cancer survival in postmenopausal women. Cancer Res. 2012;73:767–75.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Bulun SE. Uterine fibroids. N Engl J Med. 2013;369:1344–55.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • M. Veronica
    • 1
  • Altaf Ali
    • 1
  • A. Venkateshwari
    • 2
  • D. Mamata
    • 3
  • Pratibha Nallari
    • 1
  1. 1.Department of Genetics, University College of ScienceOsmania UniversityHyderabadIndia
  2. 2.Institute of Genetics and Hospital for Genetic DisordersHyderabadIndia
  3. 3.Infertility Institute and Research CenterSecunderabadIndia

Personalised recommendations