Tumor Biology

, Volume 35, Issue 6, pp 5669–5673 | Cite as

miR-146a G > C polymorphisms and risk of hepatocellular carcinoma in a Chinese population

  • Ning Cong
  • Hua Chen
  • Wen-Zhe Bu
  • Jin-Peng Li
  • Ning Liu
  • Jin-Long Song
Research Article


MicroRNAs (miRNAs) are thought to have a role in cancer development. We investigated the association among miR-146a G > C genetic variations, hepatitis B (HBV), and C (HCV) infection, and risk of hepatocellular carcinoma (HCC). Unconditional logistical regression analysis suggested that the miR-146a GG genotype and G allele carried a 2.10- (95 % confidence interval (CI) = 1.03–4.37) and 1.42-fold (95 % CI = 1.07–1.92) increased HCC risk, respectively. HBV-positive subjects carrying the miR-146a GG genotype (odds ratio (OR) = 2.95, 95 % CI = 1.31–6.81) and G allele (OR = 1.65, 95 % CI = 1.15–2.58) had an increased risk of HCC. However, the miR-146a GG genotype and G allele did not carry a significantly enhanced risk of HCC in either hepatitis-negative or HCV-infected subjects. miR-146a G > C polymorphisms appear to influence susceptibility to HCC, especially in HBV-infected patients.


miR-146a G > C Polymorphisms Hepatocellular carcinoma Risk 


  1. 1.
    International Agency for Research on Cancer. Globocan 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Accessed 1 Mar 2014.
  2. 2.
    Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis. 2002;2(7):395–403.CrossRefPubMedGoogle Scholar
  3. 3.
    Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433(7027):769–73.CrossRefPubMedGoogle Scholar
  4. 4.
    Wilfred BR, Wang WX, Nelson PT. Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways. Mol Genet Metab. 2007;91(3):209–17.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H. Stem cell division is regulated by the microRNA pathway. Nature. 2005;435(7044):974–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.CrossRefPubMedGoogle Scholar
  7. 7.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.CrossRefPubMedGoogle Scholar
  8. 8.
    Cortés-Sempere M. Ibáñez de Cáceres I. microRNAs as novel epigenetic biomarkers for human cancer. Clin Transl Oncol. 2011;13(6):357–62.CrossRefPubMedGoogle Scholar
  9. 9.
    Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.CrossRefPubMedGoogle Scholar
  10. 10.
    Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 2010;127(1):118–26.CrossRefPubMedGoogle Scholar
  11. 11.
    Wang Q, Huang Z, Ni S, Xiao X, Xu Q, Wang L, et al. Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer. PLoS One. 2012;7(9):e44398.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Mishra PJ, Bertino JR. MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics. 2009;10(3):399–416.PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Chae YS, Kim JG, Lee SJ, Kang BW, Lee YJ, Park JY, et al. A miR-146a polymorphism (rs2910164) predicts risk of and survival from colorectal cancer. Anticancer Res. 2013;33(8):3233–9.PubMedGoogle Scholar
  14. 14.
    Gao LB, Bai P, Pan XM, Jia J, Li LJ, Liang WB, et al. The association between two polymorphisms in pre-miRNAs and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2011;125(2):571–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis. 2008;29(10):1963–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Akkiz H, Bayram S, Bekar A, Akgöllü E, Üsküdar O. Genetic variation in the microRNA-499 gene and hepatocellular carcinoma risk in a Turkish population: lack of any association in a case–control study. Asian Pac J Cancer Prev. 2011;12(11):3107–12.PubMedGoogle Scholar
  17. 17.
    Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis. 2008;29(11):2126–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B, et al. Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci U S A. 2009;106(5):1502–5.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Xu Y, Li L, Xiang X, et al. Three common functional polymorphisms in microRNA encoding genes in the susceptibility to hepatocellular carcinoma: a systematic review and meta-analysis. Gene. 2013;527(2):584–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Kim WH, Min KT, Jeon YJ, et al. Association study of microRNA polymorphisms with hepatocellular carcinoma in Korean population. Gene. 2012;504(1):92–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Mihalache F, Hoblinger A, Acalovschi M, Sauerbruch T, Lammert F, Zimmer V. A common variant in the precursor miR-146a sequence does not predispose to cholangiocarcinoma in a large European cohort. Hepatobiliary Pancreat Dis Int. 2012;11(4):412–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Liu Y, Zhao JJ, Wang CM, et al. Altered expression profiles of microRNAs in a stable hepatitis B virus-expressing cell line. Chin Med J (Engl). 2009;122(1):10–4.CrossRefGoogle Scholar
  23. 23.
    Xiang Y, Fan S, Cao J, Huang S, Zhang LP. Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. Mol Biol Rep. 2012;39(6):7019–23.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ning Cong
    • 1
  • Hua Chen
    • 1
    • 2
  • Wen-Zhe Bu
    • 1
    • 2
  • Jin-Peng Li
    • 1
  • Ning Liu
    • 1
    • 2
  • Jin-Long Song
    • 1
  1. 1.Department of Surgical Oncology (Interventional Therapy)Shandong Tumor Hospital and InstituteJinanChina
  2. 2.School of Medicine and life SciencesUniversity of Jinan-Shandong Academy of Medical SciencesJinanChina

Personalised recommendations