Molecular Biology Reports

, Volume 40, Issue 1, pp 109–116 | Cite as

Quantitative assessment of the association between miR-196a2 rs11614913 polymorphism and gastrointestinal cancer risk

  • Fang Wang
  • Guo-Ping Sun
  • Yan-Feng Zou
  • Lu-Lu Fan
  • Bing Song
Article

Abstract

Published data on the association between miR-196a2 rs11614913 polymorphism and risk of gastrointestinal (GI) cancers are inconsistent among studies. To clarify the association, we performed a comprehensive literature search and a meta-analysis. We searched multiple databases to identify genetic association studies investigating the effect of miR-196a2 rs11614913 polymorphism on GI cancers with the last report up to January 18, 2012. The odds ratio (OR) and its 95 % confidence interval (95 % CI) were calculated to assess the strength of association. A total of 13 studies including 4,947 cases and 5,642 controls based on the search criteria were involved in this meta-analysis. In the overall analysis, it was suggested that variant C allele of miR-196a2 rs11614913 polymorphism could significantly increase risk of GI cancers in different genetic models (C vs T: OR = 1.17, 95 % CI = 1.07–1.28, P = 0.0008; CT + CC vs TT: OR = 1.26, 95 % CI = 1.08–1.48, P = 0.004; CC vs CT + TT: OR = 1.23, 95 % CI = 1.08–1.39, P = 0.002; CC vs TT: OR = 1.55, 95 % CI = 1.24–1.94, P = 0.0001; CT vs TT: OR = 1.20, 95 % CI = 1.02–1.40, P = 0.03). When stratified by ethnicity, we found a significant association in Asian population, as well as Caucasian population. When stratified by cancer types, we found a significant association in colorectal cancer, as well as esophageal cancer. We did not find a significant association between miR-196a2 rs11614913 polymorphism and hepatocellular carcinoma risk. For gastric cancer, a significantly increased cancer risk was observed only in homozygote comparison. This meta-analysis demonstrates that miR-196a2 rs11614913 polymorphism is significantly associated with risk of GI cancers.

Keywords

Gastrointestinal cancers miR-196a2 Genetic polymorphism Meta-analysis 

References

  1. 1.
    Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRefGoogle Scholar
  2. 2.
    Navarro Silvera SA, Mayne ST, Risch H, Gammon MD, Vaughan TL, Chow WH, Dubrow R, Schoenberg JB, Stanford JL, West AB, Rotterdam H, Blot WJ, Fraumeni JF Jr (2008) Food group intake and risk of subtypes of esophageal and gastric cancer. Int J Cancer 123:852–860PubMedCrossRefGoogle Scholar
  3. 3.
    Liu L, Zhuang W, Wang C, Chen Z, Wu XT, Zhou Y (2010) Interleukin-8 -251 A/T gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiological studies. Cytokine 50:328–334PubMedCrossRefGoogle Scholar
  4. 4.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedCrossRefGoogle Scholar
  5. 5.
    Zhu L, Yan W, Rodriguez-Canales J, Rosenberg AM, Hu N, Goldstein AM, Taylor PR, Erickson HS, Emmert-Buck MR, Tangrea MA (2011) MicroRNA analysis of microdissected normal squamous esophageal epithelium and tumor cells. Am J Cancer Res 1:574–584PubMedGoogle Scholar
  6. 6.
    Otsubo T, Akiyama Y, Hashimoto Y, Shimada S, Goto K, Yuasa Y (2011) MicroRNA-126 inhibits SOX2 expression and contributes to gastric carcinogenesis. PLoS ONE 6:e16617PubMedCrossRefGoogle Scholar
  7. 7.
    Wang W, Sun J, Li F, Li R, Gu Y, Liu C, Yang P, Zhu M, Chen L, Tian W, Zhou H, Mao Y, Zhang L, Jiang J, Wu C, Hua D, Chen W, Lu B, Ju J, Zhang X (2012) A frequent somatic mutation in CD274 3′-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding. Hum Mutat 33:480–484PubMedCrossRefGoogle Scholar
  8. 8.
    Ye Y, Wang KK, Gu J, Yang H, Lin J, Ajani JA, Wu X (2008) Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk. Cancer Prev Res (Phila) 1:460–469CrossRefGoogle Scholar
  9. 9.
    Min KT, Kim JW, Jeon YJ, Jang MJ, Chong SY, Oh D, Kim NK (2011) Association of the miR-146aC > G, 149C > T, 196a2C > T, and 499A > G polymorphisms with colorectal cancer in the Korean population. Mol Carcinog. doi:10.1002/mc.21849 Google Scholar
  10. 10.
    Zhu L, Chu H, Gu D, Ma L, Shi D, Zhong D, Tong N, Zhang Z, Wang M (2012) A functional polymorphism in miRNA-196a2 is associated with colorectal cancer risk in a Chinese population. DNA Cell Biol 31:349–353Google Scholar
  11. 11.
    Akkız H, Bayram S, Bekar A, Akgöllü E, Ulger Y (2011) A functional polymorphism in pre-microRNA-196a-2 contributes to the susceptibility of hepatocellular carcinoma in a Turkish population: a case-control study. J Viral Hepat 18:e399–e407PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang XW, Pan SD, Feng YL, Liu JB, Dong J, Zhang YX, Chen JG, Hu ZB, Shen HB (2011) Relationship between genetic polymorphism in microRNAs precursor and genetic predisposition of hepatocellular carcinoma. Zhonghua Yu Fang Yi Xue Za Zhi 45:239–243PubMedGoogle Scholar
  13. 13.
    Zhan JF, Chen LH, Chen ZX, Yuan YW, Xie GZ, Sun AM, Liu Y (2011) A functional variant in microRNA-196a2 is associated with susceptibility of colorectal cancer in a Chinese population. Arch Med Res 42:144–148PubMedCrossRefGoogle Scholar
  14. 14.
    Chen H, Sun LY, Chen LL, Zheng HQ, Zhang QF (2011) A variant in microRNA-196a2 is not associated with susceptibility to and progression of colorectal cancer in Chinese. Intern Med J. doi:10.1111/j.1445-5994.2011.02434.x Google Scholar
  15. 15.
    Li XD, Li ZG, Song XX, Liu CF (2010) A variant in microRNA-196a2 is associated with susceptibility to hepatocellular carcinoma in Chinese patients with cirrhosis. Pathology 42:669–673PubMedCrossRefGoogle Scholar
  16. 16.
    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 15:524–531PubMedCrossRefGoogle Scholar
  17. 17.
    Wang K, Guo H, Hu H, Xiong G, Guan X, Li J, Xu X, Yang K, Bai Y (2010) A functional variation in pre-microRNA-196a is associated with susceptibility of esophageal squamous cell carcinoma risk in Chinese Han. Biomarkers 15:614–618PubMedCrossRefGoogle Scholar
  18. 18.
    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 55:495–499PubMedCrossRefGoogle Scholar
  19. 19.
    Qi P, Dou TH, Geng L, Zhou FG, Gu X, Wang H, Gao CF (2010) Association of a variant in MIR 196A2 with susceptibility to hepatocellular carcinoma in male Chinese patients with chronic hepatitis B virus infection. Hum Immunol 71:621–626PubMedCrossRefGoogle Scholar
  20. 20.
    Peng S, Kuang Z, Sheng C, Zhang Y, Xu H, Cheng Q (2010) Association of microRNA-196a-2 gene polymorphism with gastric cancer risk in a Chinese population. Dig Dis Sci 55:2288–2293PubMedCrossRefGoogle Scholar
  21. 21.
    Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629–634CrossRefGoogle Scholar
  22. 22.
    Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRefGoogle Scholar
  23. 23.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRefGoogle Scholar
  24. 24.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  25. 25.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  26. 26.
    Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F, Zhang Y, Paranjape T, Zhu Y (2009) microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res 69:5970–5977PubMedCrossRefGoogle Scholar
  27. 27.
    Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304:594–596PubMedCrossRefGoogle Scholar
  28. 28.
    Qiu LX, Wang Y, Xia ZG, Xi B, Mao C, Wang JL, Wang BY, Lv FF, Wu XH, Hu LQ (2011) miR-196a2 C allele is a low-penetrant risk factor for cancer development. Cytokine 56:589–592PubMedCrossRefGoogle Scholar
  29. 29.
    Xu W, Xu J, Liu S, Chen B, Wang X, Li Y, Qian Y, Zhao W, Wu J (2011) Effects of common polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on cancer susceptibility: a meta-analysis. PLoS ONE 6:e20471PubMedCrossRefGoogle Scholar
  30. 30.
    Wang F, Ma YL, Zhang P, Yang JJ, Chen HQ, Liu ZH, Peng JY, Zhou YK, Qin HL (2012) A genetic variant in microRNA-196a2 is associated with increased cancer risk: a meta-analysis. Mol Biol Rep 39:269–275PubMedCrossRefGoogle Scholar
  31. 31.
    Chu H, Wang M, Shi D, Ma L, Zhang Z, Tong N, Huo X, Wang W, Luo D, Gao Y, Zhang Z (2011) Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies. PLoS ONE 6:e18108PubMedCrossRefGoogle Scholar
  32. 32.
    Gao LB, Bai P, Pan XM, Jia J, Li LJ, Liang WB, Tang M, Zhang LS, Wei YG, Zhang L (2011) The association between two polymorphisms in pre-miRNAs and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 125:571–574PubMedCrossRefGoogle Scholar
  33. 33.
    Guo J, Jin M, Zhang M, Chen K (2012) A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS ONE 7:e30585PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Fang Wang
    • 1
  • Guo-Ping Sun
    • 1
  • Yan-Feng Zou
    • 2
  • Lu-Lu Fan
    • 1
  • Bing Song
    • 3
  1. 1.Department of OncologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
  2. 2.Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
  3. 3.Department of CardiologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina

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