Tumor Biology

, Volume 36, Issue 5, pp 3863–3870 | Cite as

Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and clinicopathologic features in a Turkish population

  • Süleyman Bayram
  • Ahmet Taner Sümbül
  • Celal Yücel Batmacı
  • Ahmet Genç
Research Article


Overexpression of Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with cancer cell proliferation, invasion, progression, and metastasis as well as poor survival in a variety of human cancers including breast cancer (BC). A common functional single nucleotide polymorphism (SNP) rs920778 (T → C) in the intronic enhancer of the HOTAIR has been reported to influence HOTAIR expression and cancer predisposition, but the association of HOTAIR rs920778 polymorphism with BC susceptibility and clinicopathological features has yet to be investigated. We genotyped HOTAIR rs920778 polymorphism in 245 Turkish women including 123 BC patients and 122 age-matched healthy controls by a real-time polymerase chain reaction (PCR) with the TaqMan assay. We found that the CC genotype of HOTAIR rs920778 polymorphism significantly increased the risk of BC in both codominant (odds ratio (OR) = 2.12, 95 % confidence interval (CI) 1.00–4.51, P = 0.05) and recessive (OR = 2.40, 95 % CI 1.22–4.73, P = 0.01) inheritance genetic models. Our research also indicated an association between the CC genotype of HOTAIR rs920778 polymorphism and clinicopathologic features of tumor, including advanced tumor–node–metastasis (TNM) stage, larger tumor size, distant metastasis, and poor histological grade (P < 0.05). Because our findings suggest for the first time that the CC genotype of HOTAIR rs920778 polymorphism might play important roles in genetic susceptibility to BC development and aggressiveness in a Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different populations.


Breast cancer HOTAIR lncRNA HOTAIR rs920778 polymorphism Genetic susceptibility Clinicopathologic features 



The authors thank all the subjects who participated in this study.

Conflicts of interest



  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014. doi: 10.1002/ijc.29210.PubMedGoogle Scholar
  2. 2.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fraccessed on 24/11/2014.
  3. 3.
    Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001;2(3):133–40.CrossRefPubMedGoogle Scholar
  4. 4.
    Chiranjeevi P, Spurthi KM, Rani NS, Kumar GR, Aiyengar TM, Saraswati M, et al. Gelatinase B (−1562C/T) polymorphism in tumor progression and invasion of breast cancer. Tumour Biol. 2014;35(2):1351–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol. 2010;4(3):174–91.CrossRefPubMedGoogle Scholar
  6. 6.
    Yu JC, Ding SL, Chang CH, Kuo SH, Chen ST, Hsu GC, et al. Genetic susceptibility to the development and progression of breast cancer associated with polymorphism of cell cycle and ubiquitin ligase genes. Carcinogenesis. 2009;30(9):1562–70.CrossRefPubMedGoogle Scholar
  7. 7.
    Taylor JG, Choi EH, Foster CB, Chanock SJ. Using genetic variation to study human disease. Trends Mol Med. 2001;7(11):507–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.CrossRefPubMedGoogle Scholar
  9. 9.
    Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9:703–19.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Shi X, Sun M, Liu H, Yao Y, Song Y. Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett. 2013;339(2):159–66.CrossRefPubMedGoogle Scholar
  11. 11.
    Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013;45:1895–910.CrossRefPubMedGoogle Scholar
  12. 12.
    Cai B, Wu Z, Liao K, Zhang S. Long noncoding RNA HOTAIR can serve as a common molecular marker for lymph node metastasis: a meta-analysis. Tumour Biol. 2014;35:8445–50.CrossRefPubMedGoogle Scholar
  13. 13.
    Moran VA, Perera RJ, Khalil AM. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res. 2012;40:6391–400.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Tian D, Sun S, Lee JT. The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell. 2010;143:390–403.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell. 2010;39:925–38.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329:689–93.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129:1311–23.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wu Y, Zhang L, Wang Y, Li H, Ren X, Wei F, et al. Long noncoding RNA HOTAIR involvement in cancer. Tumour Biol. 2014;35(10):9531–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhang X, Zhou L, Fu G, Sun F, Shi J, Wei J, et al. The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis. 2014;35(9):2062–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Guo W, Dong Z, Bai Y, Guo Y, Shen S, Kuang G, et al. Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumour Biol. 2014. doi: 10.1007/s13277-014-2912-y.Google Scholar
  22. 22.
    Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann SurgOncol. 2010;17(6):1471–4.Google Scholar
  23. 23.
    Gauderman WJ, Morrison JM. (2006) Quanto 1.1: a computer program for power and sample size calculations for genetic-epidemiology studies,
  24. 24.
    Rodriguez S, Gaunt TR, Day IN. Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 2009;169(4):505–14.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39(6):2119–28.CrossRefPubMedGoogle Scholar
  27. 27.
    Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013;32(13):1616–25.CrossRefPubMedGoogle Scholar
  28. 28.
    Nakagawa T, Endo H, Yokoyama M, Abe J, Tamai K, Tanaka N, et al. Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. BiochemBiophys Res Commun. 2013;436(2):319–24.CrossRefGoogle Scholar
  29. 29.
    Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Lv XB, Lian GY, Wang HR, Song E, Yao H, Wang MH. Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival. PLoS One. 2013;8(5):e63516.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Süleyman Bayram
    • 1
  • Ahmet Taner Sümbül
    • 2
  • Celal Yücel Batmacı
    • 3
  • Ahmet Genç
    • 4
  1. 1.Department of Nursing, Adıyaman School of HealthAdıyaman UniversityAdıyamanTurkey
  2. 2.Department of Medical Oncology, Medical FacultyMustafa Kemal UniversityHatayTurkey
  3. 3.Department of Internal Medicine, Medical FacultyMustafa Kemal UniversityHatayTurkey
  4. 4.Vocational School of Health ServicesAdıyaman UniversityAdıyamanTurkey

Personalised recommendations