No association between single nucleotide polymorphisms in pre-mirnas and the risk of gastric cancer in Chinese population

Document Type: Original Article


1 Department of Respiratory, The First Hospital, Lanzhou University, Lanzhou 730000, China

2 Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China

3 Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China

4 Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China


Objective(s): Accumulating evidence has demonstrated that miRNAs contribute to various genetic and epigenetic modifications in the pathogenesis of gastric cancer (GC). Recent studies focused on the four single nucleotide polymorphisms (SNPs) of pre-miRNAs including rs11614913, rs3746444, rs2910164, and rs2292832. It was suggested that these four SNPs were significantly associated with the risk of GC and were described as candidate susceptibility factors. However, the previous results show conflicting findings. The aim of this study was to investigate whether these four SNPs are associated with GC in Chinese Han population.
Materials and Methods: Genotype frequencies of these four SNPs of pre-miRNAs in 220 GC patients and 530 control subjects were performed using a PCR-RFLP assay.
Results:No significant differences in genotype and allelic distribution were found in these four SNPs between GC and control subjects in the Chinese Han population. However, we found that the allelic frequency distributions of control subjects in these four SNPs were significantly different from those of the Japanese and the Koreans (All the P<0.05).
Conclusion:The four SNPs did not show any significant correlation with the development of GC in the Chinese Han population, based on the current study.


 1. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999; 80:827-841.

2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55:74-108.

3. Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet 2009; 374:477-490.

4. Bathaie SZ, Miri H, Mohagheghi MA, Mokhtari-Dizaji M, Shahbazfar AA, Hasanzadeh H. Saffron aqueous extract inhibits the chemically-induced gastric cancer progression in the Wistar Albino rat. Iran J Basic Med Sci 2013; 16:27-38.

5. Kim K, Chun KH, Suh PG, Kim IH. Alterations in cell proliferation related gene expressions in gastric cancer. Crit Rev Eukaryot Gene Expr 2011; 21:237-254.

6. Abdollahi H, Tadjrobehkar O. The role of different sugars, amino acids and few other substances in chemotaxis directed motility of helicobacter pylori. Iran J Basic Med Sci 2012; 15:787-794.

7. Parkin DM. The global health burden of infection-associated cancers in the year 2002 . Int J Cancer 2006; 118:3030-3044.

8. Resende C, Ristimaki A, Machado JC. Genetic and epigenetic alteration in gastric carcinogenesis . Helicobacter 2010; 15 Suppl 1:34-39.

9. Wroblewski LE, Peek RM, Wilson KT.Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 2010; 23:713-739.

10. Yamaguchi N, Kakizoe T. Synergistic interaction between Helicobacter pylori gastritis and diet in gastric cancer. The Lancet Oncology 2001; 2:88-94.

11. Castanotto D, Rossi JJ. The promises and pitfalls of RNA-interference-based therapeutics. Nature 2009; 457:426-433.

12. Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 2003; 113:673-676.

13. Davis MP, Abreu-Goodger C, van Dongen S, Lu D, Tate PH, Bartonicek N, et al. Large-Scale Identification of MicroRNA Targets in Murine Dgcr8-Deficient Embryonic Stem Cell Lines. PLoS One 2012; 7:e41762.

14. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 2007; 39:673-677.

15. Alizadeh M, Sadr-Nabavi A. Evaluation of a genetic test for diagnose of primary hypolactasia in northeast of iran (khorasan)

16. Heidari MM, Khatami M, Talebi AR. The POLG gene polymorphism in Iranian varicocele-associated infertility patients. Iran J Basic Med Sci 2012; 15:739-744.

17. Khorram Khorshid HR, Manoochehri M, Nasehi L, Ohadi M, Rahgozar M, Kamali R. Ccr2-64i and Ccr5 Delta32 polymorphisms in patients with late-onset Alzheimer's disease; A Study from Iran (Ccr2-64i And Ccr5 Delta32 polymorphisms in Alzheimer's disease). Iran J Basic Med Sci 2012; 15:937-944.

18. Wang DG, Fan JB, Siao CJ, Berno A, Young P, Sapolsky R, et al. Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 1998; 280:1077-1082.

19. Saunders MA, Liang H, Li WH. Human polymorphism at microRNAs and microRNA target sites. Proceedings of the National Academy of Sciences 2007; 104:3300-3305.

20. Paranjape T, Slack FJ, Weidhaas JB. MicroRNAs: tools for cancer diagnostics. Gut 2009; 58:1546-1554.

21. Karakas B, Colak D, Kaya N, Ghebeh H, Al-Qasem A, Hendrayani F, et al. Prevalence of PIK3CA mutations and the SNP rs17849079 in Arab breast cancer patients. Cancer Biol Ther 2013; 14.

22. Kuusisto KM, Akinrinade O, Vihinen M, Kankuri-Tammilehto M, Laasanen SL, Schleutker J. Copy number variation analysis in familial BRCA1/2-Pu et al Pre-miRNAs Gene Polymorphisms and Gastric CancerIran J Basic Med Sci, Vol. 17, No.2, Feb 2014 133negative finnish breast and ovarian cancer. PLoS One 2013; 8:e71802.

23. Kwon KH, Lee YC, Chung JH, Eun YG. Association study of chemokine (C-C motif) ligand 5 gene polymorphism and papillary thyroid cancer. J Invest Surg 2013.

24. Tsuchiya N, Matsui S, Narita S, Kamba T, Mitsuzuka K, Hatakeyama S, et al. Distinct cancer-specific survival in metastatic prostate cancer patients classified by a panel of single nucleotide polymorphisms of cancer-associated genes. Genes Cancer 2013; 4:54-60.

25. Huang Q, Chen D, Song S, Fu X, Wei Y, Lu J, et al. A genetic variation of the p38beta promoter region is correlated with an increased risk of sporadic colorectal cancer. Oncol Lett 2013; 6:3-8.

26. Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest 2008; 118:2600-2608.

27. Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, et al. Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis. J Clin Immunol 2011; 31:69-73.

28. Guo J, Jin M, Zhang M, Chen K. A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS One 2012; 7:e30585.

29. Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, et al. Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter 2010; 15:524-531.

30. Peng S, Kuang Z, Sheng C, Zhang Y, Xu H, Cheng Q. Association of microRNA-196a-2 gene polymorphism with gastric cancer risk in a Chinese population. Dig Dis Sci 2010; 55:2288-2293.

31. Xu W, Xu J, Liu S, Chen B, Wang X, Li Y, et al. Effects of common polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on cancer susceptibility: a meta-analysis. PLoS One 2011; 6:e20471.

32. Zhou B, Rao L, Peng Y, Wang YY, Chen Y, Song YP, et al. Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy. Clinica Chimica Acta 2010; 411:1287-1290.

33. Ahn DH, Rah H, Choi YK, Jeon YJ, Min KT, Kwack K, et al. 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 2012.

34. Zeng Y, Sun QM, Liu NN, Dong GH, Chen J, Yang L, et al. Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol 2010; 16:3578-3583.

35. Zhou FY, Zhu HX, Luo DW, Wang ML, Dong X, Hong Y, et al. A Functional polymorphism in pre-miR-146a is associated with susceptibility to gastric cancer in a chinese population. DNA Cell Biol 2012; 31:1290-1295.