Familial Cancer

, Volume 17, Issue 3, pp 459–468 | Cite as

Association between miR-146a rs2910164 polymorphism and specific cancer susceptibility: an updated meta-analysis

  • Xia Hao
  • Lingzi Xia
  • Ruoyi Qu
  • Xianglin Yang
  • Min Jiang
  • Baosen Zhou


The rapidly increasing of cancer risk nationwide and worldwide has threatened human health and caused the changes of disease and death spectrum. MicroRNA (MiRNA) as cancer biomarker on susceptibility has enjoyed a high level of concern. This article will discuss the association between miR-146 rs2910164 polymorphism and cancer susceptibility in 38 independent case-control studies from 34905 individuals. The 38 case-control studies which were searched from PubMed were used for conducting a meta-analysis. There were 14670 cases and 20235 controls. ORs and 95% CIs were used for reflecting the strength of association between miR-146a rs2910164 polymorphism and cancer susceptibility. Subgroup analysis based on the cancer type, ethnicity and study designs. All analysis were performed by using the Stata 11.0 software. MiR-146a rs2910164 polymorphism and overall cancer susceptibility were significantly uncorrelated in all genetic models. In the subgroup analysis for cancer types, miR-146a rs2910164 polymorphism was associated with the susceptibility of lung cancer (CC vs. GG: OR 1.275, 95% CI 1.117–1.455 (P = 0.000); CC + CG vs. GG: OR 1.166, 95% CI 1.052–1.293 (P = 0.003); CC vs. CG + GG: OR 1.239, 95% CI 1.116–1.375 (P = 0.000); C vs. G OR 1.151, 95% CI 1.080–1.227 (P = 0.000)) and nasopharyngeal carcinoma (CC vs. GG: OR 1.713, 95% CI 1.183–2.479 (P = 0.004); CC vs. CG + GG: OR 1.672, 95% CI 1.330–2.103 (P = 0.000); C vs. G: OR 1.400, 95% CI 1.181–1.659 (P = 0.000)), but it was not associated with hepatocellular carcinoma and gastric cancer. However, in the other subgroup analysis by ethnicity and study designs, no significant associations were found. MiR-146a rs2910164 polymorphism might be associated with the susceptibility to lung cancer and nasopharyngeal carcinoma.


MiR-146a Polymorphism Cancer Susceptibility Meta-analysis 


  1. 1.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics. 2017. CA Cancer J Clin 67(1):7–30. doi: 10.3322/caac.21387 CrossRefPubMedGoogle Scholar
  2. 2.
    Global battle against cancer won’t be won with treatment alone—effective prevention measures urgently needed to prevent cancer crisis. (2014). Cent Eur J Public Health 22(1):23–28Google Scholar
  3. 3.
    Manikandan M, Munirajan AK (2014) Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics. OMICS 18(2):142–154. doi: 10.1089/omi.2013.0098 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Macfarlane LA, Murphy PR (2010) MicroRNA: biogenesis, function and role in cancer. Current genomics 11(7):537–561. doi: 10.2174/138920210793175895 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Graves P, Zeng Y (2012) Biogenesis of mammalian microRNAs: a global view. Genomics proteomics bioinformatics 10(5):239–245. doi: 10.1016/j.gpb.2012.06.004 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Piletic K, Kunej T (2016) MicroRNA epigenetic signatures in human disease. Arch Toxicol 90(10):2405–2419. doi: 10.1007/s00204-016-1815-7 CrossRefPubMedGoogle Scholar
  7. 7.
    Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115(7):787–798CrossRefPubMedGoogle Scholar
  8. 8.
    Nicoloso MS, Sun H, Spizzo R, Kim H, Wickramasinghe P, Shimizu M, Wojcik SE, Ferdin J, Kunej T, Xiao L, Manoukian S, Secreto G, Ravagnani F, Wang X, Radice P, Croce CM, Davuluri RV, Calin GA (2010) Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility. Cancer Res 70(7):2789–2798. doi: 10.1158/0008-5472.CAN-09-3541 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Yin Z, Cui Z, Ren Y, Xia L, Li H, Zhou B (2017) MiR-146a polymorphism correlates with lung cancer risk in Chinese nonsmoking females. Oncotarget 8(2):2275–2283. doi: 10.18632/oncotarget.13722 PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang LH, Hao BB, Zhang CY, Dai XZ, Zhang F (2016) Contributions of polymorphisms in miR146a, miR196a, and miR499 to the development of hepatocellular carcinoma. Genet Mol Res 15(3). doi: 10.4238/gmr.15038582
  11. 11.
    Yadegari ZS, Akrami H, Hosseini SV, Erfani N (2016) miR-146a gene polymorphism and susceptibility to gastric cancer. Br J Biomed Sci 73(4):201–203. doi: 10.1080/09674845.2016.1233790 CrossRefPubMedGoogle Scholar
  12. 12.
    Jiang J, Jia ZF, Cao DH, Wu YH, Sun ZW, Cao XY (2016) Association of the miR-146a rs2910164 polymorphism with gastric cancer susceptibility and prognosis. Future oncology 12(19):2215–2226. doi: 10.2217/fon-2016-0224 CrossRefPubMedGoogle Scholar
  13. 13.
    Gu JY, Tu L (2016) Investigating the role of polymorphisms in miR-146a, -149, and—196a2 in the development of gastric cancer. Genet Mol Res. doi: 10.4238/gmr.15027839 CrossRefPubMedGoogle Scholar
  14. 14.
    Yin Z, Cui Z, Ren Y, Xia L, Wang Q, Zhang Y, He Q, Zhou B (2016) Association between polymorphisms in pre-miRNA genes and risk of lung cancer in a Chinese non-smoking female population. Lung Cancer 94:15–21. doi: 10.1016/j.lungcan.2016.01.013 CrossRefPubMedGoogle Scholar
  15. 15.
    Soleimani A, Ghanadi K, Noormohammadi Z, Irani S (2016) The correlation between miR-146a C/G polymorphism and UHRF1 gene expression level in gastric tumor. J Dig Dis 17(3):169–174. doi: 10.1111/1751-2980.12329 CrossRefPubMedGoogle Scholar
  16. 16.
    Xia ZG, Yin HF, Long Y, Cheng L, Yu LJ, Guo WJ, Zhu XD, Li J, Wang YN, Yang YJ, Wang JC, Jin L, Qiu LX, Wei Y (2016) Genetic variant of miR-146a rs2910164 C > G and gastric cancer susceptibility. Oncotarget 7(23):34316–34321. doi: 10.18632/oncotarget.8814 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Li D, Peng JJ, Tan Y, Chen T, Wei D, Du M, Zhang T (2015) Genetic variations in microRNA genes and susceptibility to hepatocellular carcinoma. Genet Mol Res 14(1):1926–1931. doi: 10.4238/2015.March.20.2 CrossRefPubMedGoogle Scholar
  18. 18.
    Sodhi KK, Bahl C, Singh N, Behera D, Sharma S (2015) Functional genetic variants in pre-miR-146a and 196a2 genes are associated with risk of lung cancer in North Indians. Future oncology 11(15):2159–2173. doi: 10.2217/fon.15.143 CrossRefPubMedGoogle Scholar
  19. 19.
    Yan P, Xia M, Gao F, Tang G, Zeng H, Yang S, Zhou H, Ding D, Gong L (2015) Predictive role of miR-146ars2910164 (C > G), miR-149 rs2292832 (T > C), miR-196a2 rs11614913 (T > C) and miR-499 rs3746444 (T > C) in the development of hepatocellular carcinoma. Int J Clin Exp Pathol 8(11):15177–15183PubMedPubMedCentralGoogle Scholar
  20. 20.
    Jia Y, Zang A, Shang Y, Yang H, Song Z, Wang Z, Ren L, Wei Y, Hu L, Shi H, Li H (2014) MicroRNA-146a rs2910164 polymorphism is associated with susceptibility to non-small cell lung cancer in the Chinese population. Medical oncology 31(10):194. doi: 10.1007/s12032-014-0194-2 CrossRefPubMedGoogle Scholar
  21. 21.
    Jeon HS, Lee YH, Lee SY, Jang JA, Choi YY, Yoo SS, Lee WK, Choi JE, Son JW, Kang YM, Park JY (2014) A common polymorphism in pre-microRNA-146a is associated with lung cancer risk in a Korean population. Gene 534(1):66–71. doi: 10.1016/j.gene.2013.10.014 CrossRefPubMedGoogle Scholar
  22. 22.
    Pu JY, Dong W, Zhang L, Liang WB, Yang Y, Lv ML (2014) No association between single nucleotide polymorphisms in pre-mirnas and the risk of gastric cancer in Chinese population. Iranian J Basic Med Sci 17(2):128–133Google Scholar
  23. 23.
    Kupcinskas J, Wex T, Link A, Leja M, Bruzaite I, Steponaitiene R, Juzenas S, Gyvyte U, Ivanauskas A, Ancans G, Petrenkiene V, Skieceviciene J, Kupcinskas L, Malfertheiner P (2014) Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS ONE 9(1):e87467. doi: 10.1371/journal.pone.0087467 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cong N, Chen H, Bu WZ, Li JP, Liu N, Song JL (2014) miR-146a G > C polymorphisms and risk of hepatocellular carcinoma in a Chinese population. Tumour Biol 35(6):5669–5673. doi: 10.1007/s13277-014-1750-2 CrossRefPubMedGoogle Scholar
  25. 25.
    Zhou B, Dong LP, Jing XY, Li JS, Yang SJ, Wang JP, Zhao LF (2014) Association between miR-146aG > C and miR-196a2C > T polymorphisms and the risk of hepatocellular carcinoma in a Chinese population. Tumour Biol 35(8):7775–7780. doi: 10.1007/s13277-014-2020-z CrossRefPubMedGoogle Scholar
  26. 26.
    Dikeakos P, Theodoropoulos G, Rizos S, Tzanakis N, Zografos G, Gazouli M (2014) Association of the miR-146aC > G, miR-149T > C, and miR-196a2T > C polymorphisms with gastric cancer risk and survival in the Greek population. Mol Biol Rep 41(2):1075–1080. doi:10.1007/s11033-013-2953-0CrossRefPubMedGoogle Scholar
  27. 27.
    Huang GL, Chen ML, Li YZ, Lu Y, Pu XX, He YX, Tang SY, Che H, Zou Y, Ding C, He Z (2014) Association of miR-146a gene polymorphism with risk of nasopharyngeal carcinoma in the central-southern Chinese population. J Hum Genet 59(3):141–144. doi: 10.1038/jhg.2013.135 CrossRefPubMedGoogle Scholar
  28. 28.
    Qi JH, Wang J, Chen J, Shen F, Huang JT, Sen S, Zhou X, Liu SM (2014) High-resolution melting analysis reveals genetic polymorphisms in microRNAs confer hepatocellular carcinoma risk in Chinese patients. BMC Cancer 14:643. doi: 10.1186/1471-2407-14-643 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Kou JT, Fan H, Han D, Li L, Li P, Zhu J, Ma J, Zhang ZH, He Q (2014) Association between four common microRNA polymorphisms and the risk of hepatocellular carcinoma and HBV infection. Oncol Lett 8(3):1255–1260. doi: 10.3892/ol.2014.2257 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Chu YH, Hsieh MJ, Chiou HL, Liou YS, Yang CC, Yang SF, Kuo WH (2014) MicroRNA gene polymorphisms and environmental factors increase patient susceptibility to hepatocellular carcinoma. PLoS ONE 9(2):e89930. doi: 10.1371/journal.pone.0089930 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ahn DH, Rah H, Choi YK, Jeon YJ, Min KT, Kwack K, Hong SP, Hwang SG, Kim NK (2013) Association of the miR-146aC > G, miR-149T > C, miR-196a2T > C, and miR-499A > G polymorphisms with gastric cancer risk and survival in the Korean population. Mol Carcinog 52(Suppl 1):E39–E51. doi: 10.1002/mc.21962 CrossRefPubMedGoogle Scholar
  32. 32.
    Shan YF, Huang YH, Chen ZK, Huang KT, Zhou MT, Shi HQ, Song QT, Yu ZP, Deng AM, Zhang QY (2013) miR-499A > G rs3746444 and miR-146aG > C expression and hepatocellular carcinoma risk in the Chinese population. Genet Mol Res 12(4):5365–5371. doi: 10.4238/2013.November.7.11 CrossRefPubMedGoogle Scholar
  33. 33.
    Lung RW, Wang X, Tong JH, Chau SL, Lau KM, Cheng SH, Woo JK, Woo J, Leung PC, Ng MH, Tang NL, To KF (2013) A single nucleotide polymorphism in microRNA-146a is associated with the risk for nasopharyngeal carcinoma. Mol Carcinog 52(Suppl 1):E28-38. doi: 10.1002/mc.21937 PubMedCrossRefGoogle Scholar
  34. 34.
    Hao Y-X, Wang J-P, Zhao L-F (2013) Associations between three common MicroRNA polymorphisms and hepatocellular carcinoma risk in Chinese. Asian Pac J Cancer Prev 14(11):6601–6604. doi: 10.7314/apjcp.2013.14.11.6601 CrossRefGoogle Scholar
  35. 35.
    Zhang J, Wang R, Ma YY, Chen LQ, Jin BH, Yu H, Wang JC, Gao CF, Liu J (2013) Association between single nucleotide polymorphisms in miRNA196a-2 and miRNA146a and susceptibility to hepatocellular carcinoma in a Chinese population. Asian Pac J Cancer Prev 14(11):6427–6431CrossRefPubMedGoogle Scholar
  36. 36.
    Kim WH, Min KT, Jeon YJ, Kwon C-I, Ko KH, Park PW, Hong SP, Rim KS, Kwon SW, Hwang SG, Kim NK (2012) Association study of microRNA polymorphisms with hepatocellular carcinoma in Korean population. Gene 504(1):92–97. doi: 10.1016/j.gene.2012.05.014 CrossRefPubMedGoogle Scholar
  37. 37.
    Xiang Y, Fan S, Cao J, Huang S, Zhang L-p (2012) Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. Mol Biol Rep 39(6):7019–7023. doi: 10.1007/s11033-012-1532-0 CrossRefPubMedGoogle Scholar
  38. 38.
    Zhou J, Lv R, Song X, Li D, Hu X, Ying B, Wei Y, Wang L (2012) Association between two genetic variants in miRNA and primary liver cancer risk in the Chinese population. DNA Cell Biol 31(4):524–530. doi: 10.1089/dna.2011.1340 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Zhou F, Zhu H, Luo D, Wang M, Dong X, Hong Y, Lu B, Zhou Y, Zhou J, Zhang Z, Gong W (2012) A functional polymorphism in Pre-miR-146a is associated with susceptibility to gastric cancer in a Chinese population. DNA Cell Biol 31(7):1290–1295. doi: 10.1089/dna.2011.1596 CrossRefPubMedGoogle Scholar
  40. 40.
    Vinci S, Gelmini S, Pratesi N, Conti S, Malentacchi F, Simi L, Pazzagli M, Orlando C (2011) Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers. Clin Chem Lab Med. doi: 10.1515/cclm.2011.708 PubMedCrossRefGoogle Scholar
  41. 41.
    Akkız H, Bayram S, Bekar A, Akgöllü E, Üsküdar O, Sandıkçı M (2011) No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: a case-control study. Gene 486(1–2):104–109. doi: 10.1016/j.gene.2011.07.006 CrossRefPubMedGoogle Scholar
  42. 42.
    Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, Yonemura J, Ishizuka T, Arisawa T, Hirata I (2010) Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter 15(6):524–531. doi: 10.1111/j.1523-5378.2010.00806.x CrossRefPubMedGoogle Scholar
  43. 43.
    Zeng Y (2010) Correlation betweenpre-miR-146aC/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol 16(28):3578. doi: 10.3748/wjg.v16.i28.3578 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K, Hamajima N (2010) Combined effect of miR-146a rs2910164 G/C polymorphism and toll-like receptor 4 + 3725 G/C polymorphism on the risk of severe gastric atrophy in Japanese. Dig Dis Sci 56(4):1131–1137. doi: 10.1007/s10620-010-1376-1 CrossRefPubMedGoogle Scholar
  45. 45.
    Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, Liang J, Liu P, Zhou X, Miao R, Ma H, Chen Y, Shen H (2009) A Functional Genetic variant in microRNA-196a2 Is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomark Prev 18(4):1183–1187. doi: 10.1158/1055-9965.epi-08-0814 CrossRefGoogle Scholar
  46. 46.
    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(11):2126–2131. doi: 10.1093/carcin/bgn195 CrossRefPubMedGoogle Scholar
  47. 47.
    Zhang H, Zhang Y, Yan W, Wang W, Zhao X, Ma X, Gao X, Zhang S (2017) Association between three functional microRNA polymorphisms (miR-499 rs3746444, miR-196a rs11614913 and miR-146a rs2910164) and breast cancer risk: a meta-analysis. Oncotarget 8(1):393–407. doi: 10.18632/oncotarget.13426 PubMedCrossRefGoogle Scholar
  48. 48.
    Xiang Z, Song J, Zhuo X, Li Q, Zhang X (2017) MiR-146a rs2910164 polymorphism and head and neck carcinoma risk: a meta-analysis based on 10 case-control studies. Oncotarget 8(1):1226–1233. doi: 10.18632/oncotarget.13599 PubMedCrossRefGoogle Scholar
  49. 49.
    Xie WQ, Wang XF (2017) MiR-146a rs2910164 polymorphism increases the risk of digestive system cancer: A meta-analysis. Clin Res Hepatol Gastroenterol 41(1):93–102. doi: 10.1016/j.clinre.2016.06.007 CrossRefPubMedGoogle Scholar
  50. 50.
    Sun Y, Li M (2017) Genetic polymorphism of miR-146a is associated with gastric cancer risk: a meta-analysis. Eur J Cancer Care. doi: 10.1111/ecc.12355 CrossRefGoogle Scholar
  51. 51.
    Ni Q, Ji A, Yin J, Wang X, Liu X (2015) Effects of two common polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on gastric cancer susceptibility. Gastroenterol Res Pract 2015:764163. doi: 10.1155/2015/764163 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Zhang L, Gao J, Zhou D, Bao F (2015) Lack of association of two common polymorphisms rs2910164 and rs11614913 with susceptibility to gastric cancer: a meta-analysis. Turk J Gastroenterol 26(5):378–385. doi: 10.5152/tjg.2015.6603 CrossRefPubMedGoogle Scholar
  53. 53.
    Gu YP, Yuan QY, Zhang H, Wang CJ, Zhou F (2015) Association between five common polymorphisms in microRNA genes and the risk of gastric cancer: a meta-analysis. Genet Mol Res 14(3):8375–8387. doi: 10.4238/2015.July.28.4 CrossRefPubMedGoogle Scholar
  54. 54.
    Chen ZF, Ma LL, Xue HB (2015) Common polymorphisms of the microRNA genes (miR-146a and miR-196a-2) and gastric cancer risk: an updated meta-analysis. Genet Mol Res 14(3):8589–8601. doi: 10.4238/2015.July.31.7 CrossRefPubMedGoogle Scholar
  55. 55.
    Xu L, Tang W (2016) Associations of polymorphisms in mir-196a2, mir-146a and mir-149 with colorectal cancer risk: a meta-analysis. Pathol Oncol Res 22(2):261–267. doi: 10.1007/s12253-014-9843-1 CrossRefPubMedGoogle Scholar
  56. 56.
    Ren YG, Zhou XM, Cui ZG, Hou G (2016) Effects of common polymorphisms in miR-146a and miR-196a2 on lung cancer susceptibility: a meta-analysis. J Thorac Dis 8(6):1297–1305. doi: 10.21037/jtd.2016.05.02 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Xu L, Tang W (2015) The associations of nucleotide polymorphisms in mir-196a2, mir-146a, mir-149 with lung cancer risk. Cancer Biomark 15(1):57–63. doi: 10.3233/CBM-140433 CrossRefPubMedGoogle Scholar
  58. 58.
    Chen J, Cao X, Zhang H (2015) MiR-146a rs2910164 polymorphism is associated with hepatocellular carcinoma: a meta-analysis. Int J Clin Exp Med 8(9):15852–15856PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Xia Hao
    • 1
  • Lingzi Xia
    • 1
  • Ruoyi Qu
    • 1
  • Xianglin Yang
    • 1
  • Min Jiang
    • 1
  • Baosen Zhou
    • 1
  1. 1.China Medical UniversityShenyangChina

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