Advertisement

Medical Oncology

, Volume 29, Issue 3, pp 1723–1732 | Cite as

Polymorphism in pre-miR-30c contributes to gastric cancer risk in a Chinese population

  • Yong-ping Mu
  • Xiu-lan Su
Original Paper

Abstract

To explore the association between single nucleotide polymorphisms (SNPs) A/G in pre-miR-30c and gastric cancer risk and to assess various genotypes that affected the survival of patients, we performed a hospital-based, case–control study in Inner Mongolia autonomous region of China. A total of 240 gastric cancer patients and 240 age- and sex-matched cancer-free controls collected from 2006 to 2011 were enrolled in this study. Polymorphism rs928508 in pre-miR-30c was analyzed by TaqMan SNP genotyping assay. The expression of mature miR-30c was detected by real-time quantitative reverse transcription PCR in 48 gastric cancer specimens. Survival analysis was analyzed by the Kaplan–Meier survival curves. The genotype frequencies of pre-miR-30c A/G in gastric cancer patients were obviously different from those in the controls (P = 0.022). AA genotype carriers were associated with an increased risk of gastric cancer compared with GG genotype (adjusted odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.07–3.15, P = 0.029). Moreover, the gastric cancer risk especially elevated in older individuals (aged >60 years), males, nonsmokers, and Helicobacter pylori (H. pylori)-infected individuals (adjusted OR = 2.66, 95% CI: 1.38–5.13, P = 0.004; adjusted OR = 1.90, 95% CI: 1.10–3.27, P = 0.022; adjusted OR = 1.94, 95% CI: 1.12–3.35, P = 0.018; adjusted OR = 1.83, 95% CI: 1.08–3.10, P = 0.024, respectively). Further stratified analysis indicated that AA genotype facilitated developing of gastric cancer with lymph node metastasis (adjusted OR = 2.23, 95% CI: 1.07–4.64, P = 0.032). Expression analysis detected that rs928508 AA showed a significantly increased level of mature miR-30c compared with GG or AG/GG genotype (P = 0.011 or P = 0.013). Patients with AA genotype were associated with unfavorable outcome in overall survival compared with AG/GG genotype (Log rank 5.848, P = 0.016). This study demonstrates that pre-miR-30c A/G polymorphism may be associated with an increased risk of gastric cancer in a Chinese population through altering mature miR-30c expression. However, their role as novel biomarkers for the diagnosis and prognosis of gastric diseases still needs to be systematically evaluated.

Keywords

miR-30c Polymorphisms Gastric cancer Genetic susceptibility Prognosis 

Notes

Acknowledgments

The authors thank Jia SQ for her collected samples from the First Affiliated Hospital of Inner Mongolia Medical College. This study was supported by a grant for scientific research from the Affiliated Hospital of Inner Mongolia Medical College NYFZD 2010-0008.

Conflicts of interest

None.

References

  1. 1.
    Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001;2:533–43.PubMedCrossRefGoogle Scholar
  2. 2.
    Parkin DM. International variation. Oncogene. 2004;23:6329–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.PubMedGoogle Scholar
  4. 4.
    Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.PubMedGoogle Scholar
  5. 5.
    Tamura G. Alterations of tumor suppressor and tumour-related genes in the development and progression of gastric cancer. World J Gastroenterol. 2006;12:192–8.PubMedGoogle Scholar
  6. 6.
    Correa P. Human gastric carcinogenesis: a multistep and multifactorial process–first American cancer society award lecture on cancer epidemiology and prevention. Cancer Res. 1992;52:6735–40.PubMedGoogle Scholar
  7. 7.
    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;14:1878–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347:1175–86.PubMedCrossRefGoogle Scholar
  9. 9.
    Kodama M, Murakami K, Sato R, Okimoto T, Nishizono A, Fujioka T. Helicobacter pylori-infected animal models are extremely suitable for the investigation of gastric carcinogenesis. World J Gastroenterol. 2005;11:7063–71.PubMedGoogle Scholar
  10. 10.
    Normark S, Nilsson C, NormarK BH, Hornef MW. Persistent infection with Helicobacter pylori and the development of gastric cancer. Adv Cancer Res. 2003;90:63–89.PubMedCrossRefGoogle Scholar
  11. 11.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRefGoogle Scholar
  12. 12.
    Tsuchiya S, Okuno Y, Tsujimoto G. MicroRNA: biogenetic and functional mechanisms and involvements in cell differentiation and cancer. J Pharmacol Sci. 2006;101:267–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhang B, Pan X, Cobb GP, Anderson TA. Anderson microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004;101:2999–3004.PubMedCrossRefGoogle Scholar
  15. 15.
    Duan R, Pak C, Jin P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet. 2007;16:1124–31.PubMedCrossRefGoogle Scholar
  16. 16.
    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;105:7269–74.PubMedCrossRefGoogle Scholar
  17. 17.
    Hu Z, Shu Y, Chen Y, Chen J, Dong J, Liu Y, Pan S, Xu L, Xu J, Wang Y, Dai J, Ma H, Jin G, Shen H. Genetic polymorphisms in the pre-MicroRNA flanking region and non-small-cell lung cancer survival. Am J Respir Crit Care Med. 2011;183:641–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Shen J, Ambrosone CB, Zhao H. Novel genetic variants in microRNA genes and familial breast cancer. Int J Cancer. 2009;124:1178–82.PubMedCrossRefGoogle Scholar
  19. 19.
    Sobin LH, Wittekind CH, editors. TNM classification of malignant tumors. 5th ed. New York: Wiley; 1997. p. 59–62.Google Scholar
  20. 20.
    Solcia E, Capella C, Klöppel G, Heitz PU, Sobin LH, Rosai J. Endocrine tumours of the gastrointestinal tract. In: Solcia E, Klöppel G, Sobin LH, editors. Histological typing of endocrine tumours. 2nd ed. Berlin: Springer; 2000. p. 61–8.CrossRefGoogle Scholar
  21. 21.
    Andreassen CN, Sorensen FB, Overgaard J, Alsner J. Optimisation and validation of methods to assess single nucleotide polymorphisms (SNPs) in archival histological material. Radiother Oncol. 2004;72:351–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Mishra PJ, Mishra PJ, Banerjee D, Bertino JR. MiRSNPs or MiR-polymorphisms, new players in microRNA mediated regulation of the cell. Cell Cycle. 2008;7:853–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Bertino JR, Banerjee D, Mishra PJ. Pharmacogenomics of microRNA: a miRSNP towards individualized therapy. Pharmacogenomics. 2007;8:1625–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMedCrossRefGoogle Scholar
  25. 25.
    Lewis BP, Burge CB, Bartel DP. Seed pairing, often flanked by adenosines, indicates that thousands of human genes are MicroRNA targets. Cell. 2005;12:15–20.CrossRefGoogle Scholar
  26. 26.
    Hand NJ, Master ZR, Eauclaire SF, Weinblatt DE, Matthews RP, Friedman JR. The microRNA-30 family is required for vertebrate hepatobiliary development. Gastroenterology. 2009;136:1081–90.PubMedCrossRefGoogle Scholar
  27. 27.
    Rodríguez-González FG, Sieuwerts AM, Smid M, Look MP, Meijer-van Gelder ME, de Weerd V, Sleijfer S, Martens JW, Foekens JA. MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer. Breast Cancer Res Treat. 2010;127:43–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhou R, Hu G, Liu J, Gong AY, Drescher KM, Chen XM. NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS Pathog. 2009;5:e1000681.PubMedCrossRefGoogle Scholar
  29. 29.
    Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, Kornmann M, Ju J. Prognostic values of microRNAs in colorectal cancer. Biomark Insights. 2006;2:113–21.PubMedGoogle Scholar
  30. 30.
    Wang G, Zhang H, He H, Tong W, Wang B, Liao G, Chen Z, Du C. Up-regulation of microRNA in bladder tumor tissue is not common. Int Urol Nephrol. 2010;42:95–102.PubMedCrossRefGoogle Scholar
  31. 31.
    Heinzelmann J, Henning B, Sanjmyatav J, Posorski N, Steiner T, Wunderlich H, Gajda MR, Junker K. Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol. 2011;29:367–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I, Herias V, van Leeuwen RE, Schellings MW, Barenbrug P, Maessen JG, Heymans S, Pinto YM, Creemers EE. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2009;104(2):170–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Meder B, Keller A, Vogel B, Haas J, Sedaghat-Hamedani F, Kayvanpour E, Just S, Borries A, Rudloff J, Leidinger P, Meese E, Katus HA, Rottbauer W. MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol. 2011;106:13–23.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhou R, Yuan P, Wang Y, Hunsberger JG, Elkahloun A, Wei Y, Damschroder-Williams P, Du J, Chen G, Manji HK. Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizers. Neuropsychopharmacology. 2009;34:1395–405.PubMedCrossRefGoogle Scholar
  35. 35.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A, Chapelle A. Common SNP in Pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2008;105:7269–74.PubMedCrossRefGoogle Scholar
  36. 36.
    Shen J, Ambrosone CB, DICioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis. 2008;29:1963–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Yang R, Schlehe B, Hemminki K, Sutter C, Bugert P, Wappenschmidt B, Volkmann J, Varon R, Weber BH, Niederacher D, Arnold N, Meindl A, Bartram CR, Schmutzler RK, Burwinkel B. A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk. Breast Cancer Res Treat. 2010;121:693–702.PubMedCrossRefGoogle Scholar
  38. 38.
    Catucci I, Yang R, Verderio P, Pizzamiglio S, Heesen L, Hemminki K, Sutter C, Wappenschmidt B, Dick M, Arnold N, Bugert P, Niederacher D, Meindl A, Schmutzler RK, Bartram CC, Ficarazzi F, Tizzoni L, Zaffaroni D, Manoukian S, Barile M, Pierotti MA, Radice P, Burwinkel B, Peterlongo P. Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases. Hum Mutat. 2010;31:E1052–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, Liang J, Liu P, Zhou X, Miao R, Ma H, Chen Y, Shen H. A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung. Cancer in Chinese Cancer Epidemiol Biomarkers Prev. 2009;18:1183–7.CrossRefGoogle Scholar
  40. 40.
    Dou T, Wu Q, Chen X, Ribas J, Ni X, Tang C, Huang F, Zhou L, Lu D. A polymorphism of microRNA196a genome region was associated with decreased risk of glioma in Chinese population. J Cancer Res Clin Oncol. 2010;136:1853–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Li XD, Song XX, Liu CF. A variant in microRNA-196a2 is associated with susceptibility to hepatocellular carcinoma in Chinese patients with cirrhosis. Pathology. 2010;42:669–73.PubMedCrossRefGoogle Scholar
  42. 42.
    Zeng Y, Sun QM, Liu NN, Dong GH, Chen J, Yang L, Wang B. Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol. 2010;16:3578–83.PubMedCrossRefGoogle Scholar
  43. 43.
    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;55:2288–93.PubMedCrossRefGoogle Scholar
  44. 44.
    Sun Q, Gu H, Zeng Y, Xia Y, Wang Y, Jing Y, Yang L, Wang B. Hsa-mir-27a genetic variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression. Cancer Sci. 2010;101:2241–7.PubMedCrossRefGoogle Scholar
  45. 45.
    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;14:1878–82.PubMedCrossRefGoogle Scholar
  46. 46.
    Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, Fujita H, Hasegawa S, Takagi T, Wang FY, Hirata I, Nakano H. A polymorphism of microRNA 27a genome region is associated with the development of gastric mucosal atrophy in Japanese male subjects. Dig Dis Sci. 2007;52:1691–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer. 2003;3:733–44.PubMedCrossRefGoogle Scholar
  48. 48.
    Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, Yonemura J, Ishizuka T, Arisawa T, Hirata I. Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter. 2010;15:524–31.PubMedCrossRefGoogle Scholar
  49. 49.
    Xu W, Xu J, Liu S, Chen B, Wang X, Li Y, Qian Y, Zhao W, Wu J. Effects of common polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on cancer susceptibility: a meta-analysis. PLoS One. 2011;6:e20471.PubMedCrossRefGoogle Scholar
  50. 50.
    Chu H, Wang M, Shi D, Ma L, Zhang Z, Tong N, Huo X, Wang W, Luo D, Gao Y, Zhang Z. Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies. PLoS One. 2011;6(3):e18108.PubMedCrossRefGoogle Scholar
  51. 51.
    Milne AN, Sitarz R, Carvalho R, Carneiro F, Offerhaus GJ. Early onset gastric cancer: on the road to unraveling gastric carcinogenesis. Curr Mol Med. 2007;7:15–28.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Cell BiologyCapital Medical UniversityBeijingChina
  2. 2.Clinical Medical Research Center of the Affiliated HospitalInner Mongolia Medical CollegeHohhotChina

Personalised recommendations