The miR-146a rs2910164 G > C Polymorphism and Susceptibility to Digestive Cancer in Chinese

  • Wu, Dong (Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine) ;
  • Wang, Fan (Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine) ;
  • Dai, Wei-Qi (Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine) ;
  • He, Lei (Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine) ;
  • Lu, Jie (Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine) ;
  • Xu, Ling (Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine) ;
  • Guo, Chuan-Yong (Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine)
  • Published : 2013.01.31


Background: Several studies have reported the role of the miR-146a rs2910164 G > C polymorphism as a susceptibility factor for several digestive cancers. However, the results have been controversial. Therefore, we conducted the present meta-analysis to obtain the most reliable estimate of the association. Methods: PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between miR-146a rs2910164 G > C polymorphism and digestive cancer risk. A total of four eligible studies including 3,447 cases and 5,041 controls based on the search criteria were included. Results: We observed that miR-146a rs2910164 G > C polymorphism was not significantly correlated with digestive cancer risks when all studies were pooled into the meta-analysis. While we found that miR-146a rs2910164 polymorphism was not associated with gastric cancer, it was significantly linked with hepatocellular cancer risk (the homozygote codominant model: OR = 1.40, 95% CI = 1.04-1.87). In the stratified analysis by ethnicity, significant associations were observed in Chinese population for the allele contrast model (OR = 1.25; 95% CI = 1.12-1.38), for the homozygote codominant model (OR = 1.62; 95% CI = 1.28-2.04), and for the recessive model (OR = 1.38; 95% CI = 1.16-1.64). However, studies with Asian groups presented no significant association for all genetic models. Conclusions: This meta-analysis suggests that the miR-146a rs2910164 G > C polymorphism is a low-penetrant risk factor for digestive cancers in Chinese.


Supported by : National Natural Science Foundation of China


  1. Gregory RI, Yan K, Amuthan G, et al (2004). The microprocessor complex mediates the genesis of microRNAs. Nature, 432, 235-40.
  2. Guo H, Wang K, Xiong G, et al (2010). A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han. Fam Cancer, 9, 599-603.
  3. Hishida A, Matsuo K, Goto Y, et al (2011). 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, 1131-7.
  4. Hu Z, Chen J, Tian T, et al (2008). Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest, 118, 2600-8.
  5. Jose S, George PS, Mathew A (2008). Assessment of confounding and interaction using the mantel-haenszel risk estimation method. J Cancer Prev, 9, 323-5.
  6. Kjellsson MC, Zingmark PH, Jonsson EN, Karlsson MO (2008). Comparison of proportional and differential odds models for mixed-effects analysis of categorical data. J Pharmacokinet Pharmacodyn, 35, 483-501.
  7. Lander ES, Linton LM, Birren B, et al (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860-921.
  8. Min KT, Kim JW, Jeon YJ, et al (2011). Association of the miR-146aC>G, 149C>T, 196a2C>T, and 499A>G polymorphisms with colorectal cancer in the Korean population. Mol Carcinog, 51, E65-73.
  9. Okubo M, Tahara T, Shibata T, et al (2010). Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter, 15, 524-31.
  10. Richardson K, Lai CQ, Parnell LD, Lee YC, Ordovas JM (2011). A genome-wide survey for SNPs altering microRNA seed sites identifies functional candidates in GWAS. BMC Genomics, 12, 504.
  11. Srivastava K, Srivastava A, Mittal B (2010). Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population. J Hum Genet, 55, 495-9.
  12. Wright MW, Bruford EA (2011). Naming 'junk': human non-protein coding RNA (ncRNA) gene nomenclature. Hum Genomics, 5, 90-8.
  13. Xu T, Zhu Y, Wei QK, et al (2008). A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis, 29, 2126-31.
  14. Zeng Y, Sun QM, Liu NN, et al (2010). Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol, 16, 3578-83.
  15. Zhang XW, Pan SD, Feng YL, et al (2011). Relationship between genetic polymorphism in microRNAs precursor and genetic predisposition of hepatocellular carcinoma. Zhonghua Yu Fang Yi Xue Za Zhi, 45, 239-43.
  16. Zhou J, Lv R, Song X, et al (2011). Association Between Two Genetic Variants in miRNA and Primary Liver Cancer Risk in the Chinese Population. DNA Cell Biol, 31, 524-30.
  17. Akkiz H, Bayram S, Bekar A, et al (2011). No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: a case-control study. Gene, 486, 104-9.
  18. Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
  19. Denli AM, Tops BJ, Plasterk PH, Ketting RF and Hannon GJ (2004). Processing of primary microRNAs by the microprocessor complex. Nature, 432, 231-5.
  20. Esteller M (2011). Non-coding RNAs in human disease. Nat Rev Genet, 12, 861-74.
  21. Gong J, Tong Y, Zhang HM, et al (2012). Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum Mutat, 33, 254-63.

Cited by

  1. A Genetic Variant in MiR-146a Modifies Digestive System Cancer Risk: a Meta-analysis vol.15, pp.1, 2014,
  2. Association Analysis of Single Nucleotide Polymorphisms in miR-146a and miR-196a2 on the Prevalence of Cancer in Elderly Japanese: A Case-Control Study vol.15, pp.5, 2014,
  3. A functional variant at miR-132-3p, miR-212-3p, and miR-361-5p binding site in CD80 gene alters susceptibility to gastric cancer in a Chinese Han population vol.31, pp.8, 2014,
  4. A Functional Polymorphism in the Promoter Region of MicroRNA-146a Is Associated with the Risk of Alzheimer Disease and the Rate of Cognitive Decline in Patients vol.9, pp.2, 2014,
  5. RNASEL and MIR146A SNP-SNP Interaction as a Susceptibility Factor for Non-Melanoma Skin Cancer vol.9, pp.4, 2014,
  6. Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on Gastric Cancer Susceptibility vol.2015, pp.1687-630X, 2015,
  7. Genetic polymorphism of miR-146a is associated with gastric cancer risk: a meta-analysis vol.26, pp.2, 2015,
  8. Genetic Polymorphisms in miRNAs and Susceptibility to Colorectal Cancer vol.71, pp.1, 2015,
  9. Golgi protein 73 as a biomarker for hepatocellular carcinoma: A diagnostic meta‑analysis pp.1792-1015, 2015,
  10. MiR-146a rs2910164 G/C polymorphism and gastric cancer susceptibility: a meta-analysis vol.15, pp.1, 2014,