Breast Cancer Research and Treatment

, Volume 125, Issue 2, pp 571–574 | Cite as

The association between two polymorphisms in pre-miRNAs and breast cancer risk: a meta-analysis

  • Lin-Bo Gao
  • Peng Bai
  • Xin-Min Pan
  • Jing Jia
  • Li-Juan Li
  • Wei-Bo Liang
  • Ming Tang
  • Lu-Shun Zhang
  • Yong-Gang Wei
  • Lin ZhangEmail author


Emerging evidence has shown that miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) which located in the pre-miRNA may affect the processing and then influence the expression of mature miRNA. Previous studies yielded conflicting results as to the association of two common polymorphisms in pre-miRNAs (i.e. hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913) with breast cancer. To derive a more precise effect on the association between these polymorphisms and breast cancer risk, we conducted a meta-analysis. Through retrieving PubMed for the period up to May 2010, a total of four studies were identified with 3,007 cases and 3,718 controls for has-miR-146a rs2910164 polymorphism and with 3,287 cases and 4,298 controls for hsa-miR-196a2 rs11614913 polymorphism. We found that individuals carrying CC genotype of has-miR-196a2 rs11614913 polymorphism was associated with an increased breast cancer risk in homozygote comparison (OR = 1.30; 95% CI, 1.01-1.68), and dominant model (OR = 1.11; 95% CI, 1.01-1.23). However, no significant association between has-miR-146a rs2910164 polymorphism and breast cancer risk was observed in all comparison models tested. These findings suggest that has-miR-196a2 rs11614913 polymorphism may play crucial roles in breast cancer development.


Hsa-miR-146 rs2910164 Has-miR-196a2 rs11614913 Single nucleotide polymorphism Breast cancer Meta-analysis 



This work was supported by the National Natural Science Foundation of China (No. 30901720, 30801317).

Conflict of interest statement

None of the authors has any potential financial conflict of interest related to this manuscript.


  1. 1.
    Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854CrossRefPubMedGoogle Scholar
  2. 2.
    Ruvkun G (2001) Molecular biology. Glimpses of a tiny RNA world. Science 294:797–799Google Scholar
  3. 3.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefPubMedGoogle Scholar
  4. 4.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233CrossRefPubMedGoogle Scholar
  5. 5.
    Cheng AM, Byrom MW, Shelton J, Ford LP (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290–1297CrossRefPubMedGoogle Scholar
  6. 6.
    Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86CrossRefPubMedGoogle Scholar
  7. 7.
    Xu P, Guo M, Hay BA (2004) MicroRNAs and the regulation of cell death. Trends Genet 20:617–624CrossRefPubMedGoogle Scholar
  8. 8.
    Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226–230CrossRefPubMedGoogle Scholar
  9. 9.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838CrossRefPubMedGoogle Scholar
  10. 10.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 6:259–269CrossRefPubMedGoogle Scholar
  11. 11.
    Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39:673–677CrossRefPubMedGoogle Scholar
  12. 12.
    Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070CrossRefPubMedGoogle Scholar
  13. 13.
    Lin SL, Chiang A, Chang D, Ying SY (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14:417–424CrossRefPubMedGoogle Scholar
  14. 14.
    Duan R, Pak C, Jin P (2007) Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet 16:1124–1131CrossRefPubMedGoogle Scholar
  15. 15.
    Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H (2008) A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29:1963–1966CrossRefPubMedGoogle Scholar
  16. 16.
    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 U S A 105:7269–7274CrossRefPubMedGoogle Scholar
  17. 17.
    Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W, Hua LX, Wu HF (2009) A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 70:467–472Google Scholar
  18. 18.
    Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29:2126–2131CrossRefPubMedGoogle Scholar
  19. 19.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMedGoogle Scholar
  20. 20.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  21. 21.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRefPubMedGoogle Scholar
  22. 22.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  23. 23.
    Catucci I, Yang R, Verderio P, Pizzamiglio S, Heesen L, Hemminki K, Sutter C, Wappenschmidt B, Dick M, Arnold N, Bugert P, Niederacher D, Meindl A, Schmutzler RK, Bartram CC, Ficarazzi F, Tizzoni L, Zaffaroni D, Manoukian S, Barile M, Pierotti MA, Radice P, Burwinkel B, Peterlongo P (2010) Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases. Hum Mutat 31:E1052–1057CrossRefPubMedGoogle Scholar
  24. 24.
    Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F, Zhang Y, Paranjape T, Zhu Y (2009) microRNA miR-196a–2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res 69:5970–5977CrossRefPubMedGoogle Scholar
  25. 25.
    Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J, Miao R, Wang Y, Wang X, Shen H (2009) Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat 30:79–84CrossRefPubMedGoogle Scholar
  26. 26.
    Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414CrossRefPubMedGoogle Scholar
  27. 27.
    Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103:2257–2261CrossRefPubMedGoogle Scholar
  28. 28.
    Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC (2008) Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27:5643–5647CrossRefPubMedGoogle Scholar
  29. 29.
    Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR (2009) Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 69:1279–1283CrossRefPubMedGoogle Scholar
  30. 30.
    Li Y, Vandenboom TG 2nd, Wang Z, Kong D, Ali S, Philip PA, Sarkar FH (2010) miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res 70:1486–1495CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Lin-Bo Gao
    • 1
  • Peng Bai
    • 2
  • Xin-Min Pan
    • 2
    • 3
  • Jing Jia
    • 4
  • Li-Juan Li
    • 2
  • Wei-Bo Liang
    • 2
  • Ming Tang
    • 5
  • Lu-Shun Zhang
    • 2
  • Yong-Gang Wei
    • 6
  • Lin Zhang
    • 1
    Email author
  1. 1.Laboratory of Molecular Translational Medicine, West China Second University HospitalSichuan UniversityChengduP.R.China
  2. 2.Department of Forensic Biology, West China School of Preclinical and Forensic MedicineSichuan UniversityChengduP.R.China
  3. 3.Department of Forensic PathologyHenan University of Science and TechnologyLuoyangP.R.China
  4. 4.Department of Normal PharmacologyZhejiang Academy of Medical Sciences (ZAMS)HangzhouP.R.China
  5. 5.Department of PathologyThe First People’s Hospital of Yunnan ProvinceKunmingP.R.China
  6. 6.Department of General SurgeryWest China Hospital of Sichuan UniversityChengduP.R.China

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