Association of mir-499 and mir-149 Polymorphisms with Cancer Risk in the Chinese Population: Evidence from Published Studies

  • Zhang, You-Gai (Department of Epidemiology, College of Public Health, Zhengzhou University) ;
  • Shi, Jian-Xiang (Department of Epidemiology, College of Public Health, Zhengzhou University) ;
  • Song, Chun-Hua (Department of Epidemiology, College of Public Health, Zhengzhou University) ;
  • Wang, Peng (Department of Epidemiology, College of Public Health, Zhengzhou University) ;
  • Dai, Li-Ping (Department of Epidemiology, College of Public Health, Zhengzhou University) ;
  • Zhang, Jian-Ying (Department of Epidemiology, College of Public Health, Zhengzhou University) ;
  • Shi, Jia-Chen (Department of Epidemiology, College of Public Health, Zhengzhou University)
  • Published : 2013.04.30


Meta-analyses have shown that microRNA polymorphisms have variable effects in different population. Yet, no meta-analysis investigated the association of two common polymorphisms of miRNA, mir-499 rs3746444 polymorphism and mir-149 rs2292832 polymorphism, with cancer risk in the Chinese population. We searched the PubMed, Web of Knowledge, MEDLINE, CNKI databases, as well as Cochrane library, updated on December 31, 2012 for assays regarding cancer risk association with these two common polymorphisms in the present meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to explore the strength of associations. The results showed that rs3746444 polymorphism was associated with increased cancer risk (dominant model: GG/AG vs. AA: OR = 1.43, 95% CI: 1.14-1.80; recessive model: GG vs. AG/AA: OR = 1.54, 95% CI: 1.04-2.30; homozygote model: GG vs. AA: OR = 1.69, 95% CI: 1.10-2.60; heterozygote model: AG vs. AA: OR = 1. 35, 95% CI: 1.09-1.67), and rs3746444 was associated with liver cancer in the subgroup of cancer types. For the rs2292832 polymorphism, the results showed no significant risk association in both overall pooled analysis and subgroup of cancer types, smoking status, gender and tea drinking status in the Chinese population. This meta-analysis suggested that the rs3746444 GG genotype is associated with increased cancer risk, especially liver cancer, while the rs2292832 polymorphism showed no association with cancer risk in Chinese.


Supported by : National Natural Science Foundation of China


  1. Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
  2. Calin GA, Sevignani C, Dumitru CD, et al (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA, 101, 2999-3004.
  3. Chen LT, Xu SD, Xu H, et al (2012). MicroRNA-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis. Med Oncol, 29, 1673-80.
  4. Chu YH, Tzeng SL, Lin CW, et al (2012). Impacts of microRNA gene polymorphisms on the susceptibility in oral cancer. PLoS One, 7, e39777.
  5. Egger M, Davey Smith G, Schneider M, et al (1998). Bias in metaanalysis detected by a simple, graphical test. Brit Med J, 316, 471.
  6. Fabbri M, Calore F, Paone A, et al (2013). Epigenetic regulation of miRNAs in cancer. Adv Exp Med Biol, 754, 137-48.
  7. Filipowicz W, Bhattacharyya SN, Sonenberg N et al (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet, 9, 102-14 .
  8. Handoll HH (2006).Systematic reviews on rehabilitation interventions. Arch Phys Med Rehab, 87, 875.
  9. He B, Pan Y, Cho WC, et al (2012). The Association between Four Genetic Variants in MicroRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and Cancer Risk: Evidence from Published Studies. PLoS One, 7, e49032.
  10. Hu Z, Liang J, Wang Z, et al (2009). Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat, 30, 79-84.
  11. Ivanovska I, Ball AS, Diaz RL, et al (2008). MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression. Mol Cell Biol, 28, 2167-74.
  12. Jang MJ, Kim JW, Min KT, et al (2011). Prognostic significance of microRNA gene polymorphisms in patients with surgically resected colorectal cancer. Exp Ther Med, 2, 1127-32.
  13. Kim WH, Min KT, Jeon YJ, et al (2012) Association study of microRNA polymorphisms with hepatocellular carcinoma in Korean population. Gene, 504, 92-7.
  14. Lewis BP, Burge CB, Bartel DP (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120 , 15-20.
  15. Ling XX, Li YY, Yang L, et al (2011). Genetic variant in seed region of hsa-miR-499-3p( rs3746444 A>G) increases risk of lung cancer. Chin J Public Health, 27, 3.
  16. Liu Z, Li G, Wei S, et al (2012).Genetic variants in selected premicroRNA genes and the risk of squamous cell carcinoma of the head and neck. Cancer, 116, 4753-60.
  17. Lu Y, Thomson JM, Wong HY, et al (2007). Transgenic overexpression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol, 310, 442-53.
  18. Midgette AS, Wong JB, Beshansky JR, et al (1994). Costeffectiveness of streptokinase for acute myocardial infarction: A combined meta-analysis and decision analysis of the effects of infarct location and of likelihood of infarction. Med Decis Making, 14, 108-117.
  19. Pan SJ, Zhan SK, Pei BG, et al (2012). MicroRNA-149 inhibits proliferation and invasion of glioma cells via blockade of AKT1 signaling. Int J Immunopathol Pharmacol, 25, 871-81.
  20. Qiu MT, Hu JW, Ding XX, et al (2012). Hsa-miR-499 rs3746444 polymorphism contributes to cancer risk: a meta-analysis of 12 studies. PLoS One, 7, e50887.
  21. Ryan BM, Robles AI , Harris CC (2010). Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer, 10, 389-402.
  22. Srivastava K , Srivastava A (2012). Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk. PLoS One, 7, e50966.
  23. Tu HF, Liu CJ, Chang CL, et al (2012). The Association between Genetic Polymorphism and the Processing Efficiency of Affects the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma. PLoS One, 7, e51606.
  24. Tian T, Shu Y, Chen J, et al (2009).A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev, 18, 1183-7.
  25. Vasudevan S, Tong Y, Steitz JA (2007). Switching from repression to activation: microRNAs can up-regulate translation. Science, 318, 1931-4 .
  26. Wang F, Sun G, Zou Y, et al (2012). Association of microRNA-499 rs3746444 polymorphism with cancer risk: evidence from 7188 cases and 8548 controls. PLoS One, 7, e45042.
  27. Wang JX, Jiao JQ, Li Q, et al (2011). miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat Med, 17, 71-8.
  28. Wang F, Ma YL, Zhang P, et al (2013). SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer. J Pathol, 229, 12-24.
  29. Wang R, Wang ZX, Yang JS, et al (2011). MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14). Oncogene, 30, 2644-58.
  30. Xiang Y, Fan S, Cao J, et al (2012). Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. Mol Biol Rep, 39, 7019-23.
  31. Zhang J, Liu YF , Gan Y (2012). Lack of association between miR-149 C>T polymorphism and cancer susceptibility: a meta-analysis based on 4,677 cases and 4,830 controls. Mol Biol Rep, 39, 8749-53.
  32. Zhang M, Jin M, Yu Y, et al (2012).Associations of miRNA polymorphisms and female physiological characteristics with breast cancer risk in Chinese population. Eur J Cancer Care, 21, 274-80.
  33. Zhang MW, Jin MJ, Yu YX, et al (2012).Associations of lifestyle-related factors, hsa-miR-149 and hsa-miR-605 gene polymorphisms with gastrointestinal cancer risk. Mol Carcinogen, 51, E21-31.
  34. Zhang MW, Yu YX, Jin MJ, et al (2011). Association of miR-605 and miR-149 genetic polymorphism with related risk factors of lung cancer susceptibility. Zhejiang Univ(Med Sci), 40, 265-71.
  35. Zhou B, Wang K, Wang Y, et al (2011). Common genetic polymorphisms in pre-microRNAs and risk of cervical squamous cell carcinoma. Mol Carcinogen, 50, 499-505.
  36. Zhou J, Lv R, Song X, et al (2012). Association between two genetic variants in miRNA and primary liver cancer risk in the Chinese population. DNA Cell Biol, 31, 524-30.

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