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Cancer Causes & Control

, Volume 25, Issue 11, pp 1571–1575 | Cite as

Association between genetic variant in hsa-miR-146a gene and prostate cancer progression: evidence from Serbian population

  • Zorana Z. Nikolić
  • Dušanka Lj. Savić Pavićević
  • Vinka D. Vukotić
  • Saša M. Tomović
  • Snežana J. Cerović
  • Nataša Filipović
  • Stanka P. Romac
  • Goran N. Brajušković
Brief report

Abstract

Purpose

Two previous studies of association between rs2910164 in miR-146a gene and prostate cancer (PCa) risk have provided opposing results. Furthermore, no evidence of association of this SNP with standard prognostic parameters of PCa progression was obtained in mentioned studies. The main aim of this study was to evaluate the possible association between PCa onset and progression to a more aggressive form, since it has not been assessed in a population of European descent.

Methods

In this study, 286 samples of peripheral blood were obtained from patients with PCa, while the control group comprised 199 volunteers derived from general population who gave samples of buccal swabs. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS), and clinical stage were determined. Genotyping of rs2910164 was performed using Taqman® SNP Genotyping Assay. Analysis of SNP association was done using PLINK and SNPStats software.

Results

rs2910164 showed no association with PCa risk. Nevertheless, heterozygous genotype was found to be associated with higher GS, as well as with the presence of distant metastases. rs2910164 was also shown to be associated with cancer aggressiveness (p = 0.0067; ORGC = 2.22, 95 %CI 1.24–3.97; ORCC = 0.47, 95 %CI 0.13–1.68).

Conclusions

Our results show no evidence of association between rs2910164 and PCa risk in Serbian population. Conversely, this variant was found to be associated with PCa aggressiveness.

Keywords

Association study microRNA miR-146a Prostate cancer Single-nucleotide polymorphism 

Notes

Acknowledgments

The research was supported by the Ministry of Education, Science and Technological Development of Serbia (Project No. 173016).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN. Int J Cancer 127(12):2893–2917PubMedCrossRefGoogle Scholar
  2. 2.
    Alshalalfa M, Bader GD, Goldenberg A, Morris Q, Alhajj R (2012) Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study. BMC Syst Biol 6:112PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Farazi TA, Hoell JI, Morozov P, Tuschl T (2013) MicroRNAs in human cancer. Adv Exp Med Biol 774:1–20PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Shenouda SK, Alaahri SK (2009) MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev 28:369–378PubMedCrossRefGoogle Scholar
  5. 5.
    Xu B, Feng NH, Li PC et al (2010) A functional polymorphism in pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 70(5):467–472PubMedGoogle Scholar
  6. 6.
    George GP, Gangwar R, Mandal RK, Sankhwar SN, Mittal RD (2011) Genetic variation in microRNA genes and prostate cancer risk in North Indian population. Mol Biol Rep 38(3):1609–1615PubMedCrossRefGoogle Scholar
  7. 7.
    Medeiros RM, Morais A, Vasconcelos A et al (2002) Outcome in prostate cancer: association with endothelial nitric oxide synthase Glu-Asp298 polymorphism at exon 7. Clin Cancer Res 8(11):3433–3437PubMedGoogle Scholar
  8. 8.
    Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81(3):559–575PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Solé X, Guinó E, Valls J, Iniesta R, Moreno V (2006) SNPstats: a web tool for the analysis of association studies. Bioinformatics 22(15):1928–1929PubMedCrossRefGoogle Scholar
  10. 10.
    Wigginton JE, Cutler DJ, Abecasis GR (2005) A note on exact tests of Hardy–Weinberg equilibrium. Am J Hum Genet 76(5):887–893PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A (2008) Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105(20):7269–7274PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Pastrello C, Polesel J, Della Puppa L, Viel A, Maestro R (2010) Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1/BRCA2-negative familial breast and ovarian cancer patients. Carcinogenesis 31(12):2124–2126PubMedCrossRefGoogle Scholar
  13. 13.
    Yue C, Wang M, Ding B et al (2011) Polymorphism of the pre-miR-146a is associated with risk of cervical cancer in a Chinese population. Gynecol Oncol 122(1):33–37PubMedCrossRefGoogle Scholar
  14. 14.
    Guo H, Wang K, Xiong G et al (2010) A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han. Fam Cancer 9(4):599–603PubMedCrossRefGoogle Scholar
  15. 15.
    Xu T, Zhu Y, Wei QK et al (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29(11):2126–2131PubMedCrossRefGoogle Scholar
  16. 16.
    Zeng Y, Sun QM, Liu NN et al (2010) Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol 16(28):3578–3583PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Jazdzewski K, Liyanarachchi S, Swierniak M et al (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106(5):1502–1505PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Lin SL, Chiang A, Chang D, Ying SY (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14(3):417–424PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Xu B, Wang N, Wang X et al (2012) MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. Prostate 72(11):1171–1178PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Zorana Z. Nikolić
    • 1
  • Dušanka Lj. Savić Pavićević
    • 1
  • Vinka D. Vukotić
    • 2
  • Saša M. Tomović
    • 3
  • Snežana J. Cerović
    • 4
  • Nataša Filipović
    • 2
  • Stanka P. Romac
    • 1
  • Goran N. Brajušković
    • 1
  1. 1.Faculty of BiologyUniversity of BelgradeBelgradeSerbia
  2. 2.Department of UrologyClinical Centre “dr Dragiša Mišović”BelgradeSerbia
  3. 3.Clinical Department of SurgeryClinical Centre “Zvezdara”BelgradeSerbia
  4. 4.Institute of PathologyMilitary Medical AcademyBelgradeSerbia

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