Skip to main content

Advertisement

SpringerLink
Log in

A functional HOTAIR rs12826786 C>T polymorphism is associated with breast cancer susceptibility and poor clinicopathological characteristics in a Turkish population: a hospital-based case–control study

  • Original Article
  • Published:
Tumor Biology

Abstract

Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is pervasively overexpressed and correlated with tumor invasion, progression, metastasis, and poor prognosis in various human cancers including breast cancer (BC) that plays a role as an oncogenic molecule. A common functional single-nucleotide polymorphism (SNP) (rs12826786 C>T) at the HOTAIR promoter has been reported to influence HOTAIR expression and gastric adenocarcinoma susceptibility, but relation of HOTAIR rs12826786 C>T polymorphism with BC susceptibility and clinicopathological characteristics has yet to be reported. To explore the association of the HOTAIR rs12826786 C>T polymorphism with the risk of BC in a Turkish population, a hospital-based case–control study was carried out consisting of 123 BC patients and 122 age-matched healthy controls. HOTAIR rs12826786 C>T polymorphism was determined by real-time polymerase chain reaction (PCR) using TaqMan assay. We found that women carrying TT genotype of HOTAIR rs12826786 C>T polymorphism had an increased risk of developing BC in both codominant (odds ratio (OR) = 2.24, 95 % confidence interval (CI) 1.05–4.81, P = 0.02) and recessive (OR = 2.49, 95 % CI 1.25–4.97, P = 0.008) inheritance models. Moreover, TT genotype of HOTAIR rs12826786 C>T polymorphism was significantly related with multiple clinicopathological characteristics concerned with worse BC progression such as advanced TNM stage (III and IV), larger tumor size (T3 and T4), and distant metastasis (M1), as well as poor histological grade (III) (P < 0.05). Because of our results put forward for the first time that TT genotype of HOTAIR rs12826786 C>T polymorphism might play crucial roles in genetic susceptibility and poor prognosis for BC in Turkish population, further independent studies are needed to confirm our results in a larger series, as well as in patients of distinct populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sonnenschein C, Soto MA. The aging of the 2000 and 2011 hallmarks of cancer reviews: a critique. J Biosci. 2013;38(3):651–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.fr, accessed on 29/10/2015.

  3. Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001;2(3):133–40.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  5. Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol. 2010;4(3):174–91.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  7. Taylor JG, Choi EH, Foster CB, Chanock SJ. Using genetic variation to study human disease. Trends Mol Med. 2001;7(11):507–12.

    Article  CAS  PubMed  Google Scholar 

  8. Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.

    Article  CAS  PubMed  Google Scholar 

  9. Bhan A, Mandal SS. LncRNA HOTAIR: a master regulator of chromatin dynamics and cancer. Biochim Biophys Acta. 2015;1856(1):151–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Loewen G, Zhuo Y, Zhuang Y, Jayawickramarajah J, Shan B. lincRNA HOTAIR as a novel promoter of cancer progression. J Can Res Updates. 2014;3(3):134–40.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhang S, Chen S, Yang G, Gu F, Li M, Zhong B, et al. Long noncoding RNA HOTAIR as an independent prognostic marker in cancer: a meta-analysis. PLoS One. 2014;9:e105538.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bayram S, Sümbül AT, Batmacı CY, Genç A. Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and clinicopathologic features in a Turkish population. Tumour Biol. 2015;36(5):3863–70.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. Du M, Wang W, Jin H, Wang Q, Ge Y, Lu J, et al. The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population. Oncotarget. 2015;6(31):31255–62.

    PubMed  PubMed Central  Google Scholar 

  16. Bayram S, Ülger Y, Sümbül AT, Kaya BY, Rencüzoğulları A, Genç A, et al. A functional HOTAIR rs920778 polymorphism does not contributes to gastric cancer in a Turkish population: a case–control study. Familial Cancer. 2015;14(4):561–7. doi:10.1007/s10689-015-9813-0.

  17. Pan W, Liu L, Wei J, Ge Y, Zhang J, Chen H, et al. A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol Carcinog. 2015. doi:10.1002/mc.22261.

    Google Scholar 

  18. 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. 2015;36(4):2845–54.

    Article  CAS  PubMed  Google Scholar 

  19. Xue Y, Gu D, Ma G, Zhu L, Hua Q, Chu H, et al. Genetic variants in lncRNA HOTAIR are associated with risk of colorectal cancer. Mutagenesis. 2015;30(2):303–10.

    Article  CAS  PubMed  Google Scholar 

  20. 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 Surg Oncol. 2010;17(6):1471–4.

    Article  PubMed  Google Scholar 

  21. Gauderman WJ, Morrison JM. Quanto 1.1: a computer program for power and sample size calculations for genetic-epidemiology studies, http://hydra.usc.edu/gxe, 2006.

  22. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 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.

    Article  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. 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. Biochem Biophys Res Commun. 2013;436(2):319–24.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Dr. Bayram and Dr. Sümbül designed the study. Dr. Sümbül applied for Research Ethics Board approval. Dr. Sümbül and Dr. Dadaş recruited the 123 breast cancer patients and 122 age-matched healthy controls and collected the data. Dr. Bayram was carried out assays. Dr. Bayram and Dr. Sümbül prepared the manuscript draft with important intellectual input from Dr. Dadaş. The authors thank all the subjects who participated in this study.

Author information

Authors and Affiliations

  1. Department of Nursing, Adıyaman School of Health, Adıyaman University, 02040, Adıyaman, Turkey

    Süleyman Bayram

  2. Department of Medical Oncology, Faculty of Medicine, Başkent University, 01250, Adana, Turkey

    Ahmet Taner Sümbül

  3. Department of Thoracic Surgery, Faculty of Medicine, Adıyaman University, 02040, Adıyaman, Turkey

    Erdoğan Dadaş

Authors
  1. Süleyman Bayram
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmet Taner Sümbül
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erdoğan Dadaş
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Süleyman Bayram.

Ethics declarations

Conflicts of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bayram, S., Sümbül, A.T. & Dadaş, E. A functional HOTAIR rs12826786 C>T polymorphism is associated with breast cancer susceptibility and poor clinicopathological characteristics in a Turkish population: a hospital-based case–control study. Tumor Biol. 37, 5577–5584 (2016). https://doi.org/10.1007/s13277-015-4430-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4430-y

Keywords

Search

Navigation