Research Paper Volume 9, Issue 2 pp 381—392

MiR-146a and miR-196a-2 polymorphisms are associated with hepatitis virus-related hepatocellular cancer risk: a meta-analysis

Tian Tian 1, *, , Meng Wang 1, *, , Wenge Zhu 2, , Zhi-Ming Dai 3, , Shuai Lin 1, , Peng-Tao Yang 1, , Xing-Han Liu 1, , Kang Liu 1, , Yu-Yao Zhu 1, , Yi Zheng 1, , Meng Liu 1, , Zhi-Jun Dai 1, ,

  • 1 Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
  • 2 Department of Biochemistry and Molecular Medicine, The George Washington University Medical School, Washington, DC 20037, USA
  • 3 Department of Anesthesia, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
* Equal contribution

received: November 30, 2016 ; accepted: January 15, 2017 ; published: January 31, 2017 ;
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Previous studies have investigated the role of miR-146a rs2910164 and miR-196a-2 rs11614913 polymorphisms in hepatocellular carcinoma (HCC) susceptibility, but the results are contradictory and few specifically studied hepatitis virus-related HCC. Therefore, we conducted a meta-analysis to evaluate the association between these two polymorphisms and hepatitis virus-related HCC risk. We performed a systematical search in EMBASE, PubMed, Web of Science, CNKI and Wanfang databases as of 25th November, 2016. Finally, we assessed 14 studies involving 3852 cases and 5275 controls. Our results suggest that rs2910164 has a significant association with increased hepatitis virus-related HCC risk in allelic, homozygous, heterozygous, and dominant models (CG+GG vs. CC: OR=1.22, 95% CI=1.06-1.39, P=0.004), particularly in Chinese and HBV-related HCC subgroups. Conversely, rs11614913 was associated with lower hepatitis virus-related HCC risk in the overall analysis under allelic (T vs. C: OR=0.85, 95% CI=0.74-0.98, P=0.02), homozygous, dominant and recessive models. Subgroup analyses showed decreased risk in Chinese, HBV- and HCV-related HCC. In conclusion, miR-146a C>G (rs2910164) can increase HBV-related HCC risk while miR-196a-2 C>T (rs11614913) may decrease the risk of HBV- and HCV-related HCC, especially in the Chinese population. Further, large-scale studies including other races are required to confirm these findings.


HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HCV: hepatitis C virus; miRNA: microRNA; SNP: Single nucleotide polymorphism; OR: odds ratio; CI: confidence interval; HWE: Hardy-Weinberg equilibrium.