Digestive Diseases and Sciences

, Volume 55, Issue 8, pp 2288–2293

Association of MicroRNA-196a-2 Gene Polymorphism with Gastric Cancer Risk in a Chinese Population

  • Sheng Peng
  • Zhongshen Kuang
  • Chenyi Sheng
  • Yan Zhang
  • Hang Xu
  • Qinghong Cheng
Original Article



It has been proposed that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) could affect the expression of the miRNA and contribute to the susceptibility of human tumors. However, the role of genetic variant (T/C) in miR-196a-2 in gastric cancer susceptibility is still unknown.


To evaluate the association between genetic polymorphism of miR-196a-2 (rs11614913) and risk of gastric cancer, a hospital-based case–control study was conducted in a Chinese population.


The miR-196a-2 polymorphism was determined using the method of polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) in 213 gastric cancer patients and 213 age- and sex-matched controls.


In the present study, we found that a significantly increased risk of gastric cancer in subjects with the variant homozygote CC of miR-196a-2 compared with wild-type homozygote TT and heterozygote CT carriers (adjusted odds ratio (OR) = 1.57, 95% confidence interval (CI) = 1.03–2.39, P = 0.038). Stratified analyses indicated that the variant homozygote CC genotype had a strong association with lymph node metastasis of gastric cancer (adjusted OR = 2.25, 95% CI = 1.21–4.18, P = 0.011).


These findings suggest that the genetic variant within miR-196a-2 could play an important role in the development and progression of gastric cancer. We expect the findings may be helpful to better understand the mechanism of gastric carcinogenesis.


microRNA-196a-2 Gastric cancer Polymorphism Carcinogenesis 



Confidence interval


Odds ratio


Polymerase chain reaction




Single nucleotide polymorphism


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Wu MS, Chen CJ, Lin JT. Host–environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1878–1882.CrossRefPubMedGoogle Scholar
  3. 3.
    Correa P, Schneider BG. Etiology of gastric cancer: what is new? Cancer Epidemiol Biomarkers Prev. 2005;14:1865–1868.CrossRefPubMedGoogle Scholar
  4. 4.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297.CrossRefPubMedGoogle Scholar
  5. 5.
    Carthew RW. Gene regulation by microRNAs. Curr Opin Genet Dev. 2006;16:203–208.CrossRefPubMedGoogle Scholar
  6. 6.
    Iwai N, Naraba H. Polymorphisms in human pre-miRNAs. Biochem Biophys Res Commun. 2005;331:1439–1444.CrossRefPubMedGoogle Scholar
  7. 7.
    Yu Z, Li Z, Jolicoeur N, et al. Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers. Nucleic Acids Res. 2007;35:4535–4541.CrossRefPubMedGoogle Scholar
  8. 8.
    Hu Z, Chen J, Tian T, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 2008;118:2600–2608.CrossRefPubMedGoogle Scholar
  9. 9.
    Tian T, Shu Y, Chen J, et al. A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev. 2009;18:1183–1187.CrossRefPubMedGoogle Scholar
  10. 10.
    Gianfagna F, De Feo E, van Duijn CM, Ricciardi G, Boccia S. A systematic review of meta-analyses on gene polymorphisms and gastric cancer risk. Curr Genomics. 2008;9:361–374.CrossRefPubMedGoogle Scholar
  11. 11.
    Roberts-Thomson IC, Butler WJ. Polymorphism and gastric cancer. J Gastroenterol Hepatol. 2005;20:793–794.CrossRefPubMedGoogle Scholar
  12. 12.
    Mishra PJ, Mishra PJ, Banerjee D, Bertino JR. MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell: introducing microRNA pharmacogenomics. Cell Cycle. 2008;7:853–858.PubMedGoogle Scholar
  13. 13.
    Saunders MA, Liang H, Li WH. Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA. 2007;104:3300–3305.CrossRefPubMedGoogle Scholar
  14. 14.
    Wu M, Jolicoeur N, Li Z, et al. Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs. Carcinogenesis. 2008;29:1710–1716.CrossRefPubMedGoogle Scholar
  15. 15.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2008;105:7269–7274.CrossRefPubMedGoogle Scholar
  16. 16.
    Xu T, Zhu Y, Wei QK, et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis. 2008;29:2126–2131.CrossRefPubMedGoogle Scholar
  17. 17.
    Hu Z, Liang J, Wang Z, et al. Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat. 2009;30:79–84.CrossRefPubMedGoogle Scholar
  18. 18.
    Ye Y, Wang KK, Gu J, et al. Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk. Cancer Prev Res (Phila Pa). 2008;1:460–469.Google Scholar
  19. 19.
    Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–838.CrossRefPubMedGoogle Scholar
  20. 20.
    Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006;103:2257–2261.CrossRefPubMedGoogle Scholar
  21. 21.
    Iorio MV, Ferracin M, Liu CG, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–7070.CrossRefPubMedGoogle Scholar
  22. 22.
    Schimanski CC, Frerichs K, Rahman F, et al. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World J Gastroenterol. 2009;15:2089–2096.CrossRefPubMedGoogle Scholar
  23. 23.
    Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353:1793–1801.CrossRefPubMedGoogle Scholar
  24. 24.
    Duan R, Pak C, Jin P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet. 2007;16:1124–1131.CrossRefPubMedGoogle Scholar
  25. 25.
    Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science. 2004;304:594–596.CrossRefPubMedGoogle Scholar
  26. 26.
    Luthra R, Singh RR, Luthra MG, et al. MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene. 2008;27:6667–6678.CrossRefPubMedGoogle Scholar
  27. 27.
    Yang YC, Wang SW, Wu IC, et al. A tumorigenic homeobox (HOX) gene expressing human gastric cell line derived from putative gastric stem cell. Eur J Gastroenterol Hepatol. 2009;21:1016–1023.CrossRefPubMedGoogle Scholar
  28. 28.
    Yu G, Wang J, Chen Y, et al. Tissue microarray analysis reveals strong clinical evidence for a close association between loss of annexin A1 expression and nodal metastasis in gastric cancer. Clin Exp Metastasis. 2008;25:695–702.CrossRefPubMedGoogle Scholar
  29. 29.
    Hung RJ, Boffetta P, Brennan P, et al. Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis. 2004;25:973–978.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Sheng Peng
    • 1
  • Zhongshen Kuang
    • 2
  • Chenyi Sheng
    • 3
  • Yan Zhang
    • 1
  • Hang Xu
    • 2
  • Qinghong Cheng
    • 2
  1. 1.Department of AnesthesiologyThe Fourth Affiliated Hospital of Soochow UniversityWuxiPeople’s Republic of China
  2. 2.Intensive Care Unit of the First Affiliated Hospital of Medical CollegeShihezi UniversityShiheziPeople’s Republic of China
  3. 3.Department of General SurgeryAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China

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