Tumor Biology

, Volume 34, Issue 3, pp 1919–1923

Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma

Research Article


Growing evidence indicates that tumor suppressor gene TP-53 and non-coding RNA miR-34b/c independently and/or jointly play crucial roles in carcinogenesis. We hypothesized that the polymorphisms of rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72-Pro may be related to the risk of nasopharyngeal carcinoma (NPC). We performed a case–control study between 217 patients with NPC and 360 healthy controls in a Chinese population using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. A significantly increased risk of NPC was observed in the miR-34b/c rs4938723 CT/CC genotypes compared with the TT genotype (adjusted OR = 1.44, 95 % CI 1.02–2.03, p = 0.04), and also the C allele (adjusted OR = 1.33, 95 % CI 1.04–1.70, p = 0.03). The gene–gene interaction of miR-34b/c rs4938723 and TP-53 Arg72-Pro showed that the combined genotypes of rs4938723CT/CC and TP-53CG/CC increased the risk of NPC (rs4938723CT/CC + TP-53CG/CC vs. rs4938723 TT + TP-53 CG/CC: OR = 1.58, 95 % CI 1.04–2.42, p = 0.03). These findings suggest that miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may singly or collaboratively contribute to the risk of NPC.


Nasopharyngeal carcinoma miR-34b/c TP-53 Genetic polymorphism 


  1. 1.
    Bei JX, Li Y, Jia WH, Feng BJ, Zhou G, Chen LZ, et al. A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nat Genet. 2010;42(7):599–603.PubMedCrossRefGoogle Scholar
  2. 2.
    Chang CM, Yu KJ, Mbulaiteye SM, Hildesheim A, Bhatia K. The extent of genetic diversity of Epstein–Barr virus and its geographic and disease patterns: a need for reappraisal. Virus Res. 2009;143(2):209–21.PubMedCrossRefGoogle Scholar
  3. 3.
    Cho WC. Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer. 2007;6:1.PubMedCrossRefGoogle Scholar
  4. 4.
    Su CK, Wang CC. Prognostic value of Chinese race in nasopharyngeal cancer. Int J Radiat Oncol Biol Phys. 2002;54(3):752–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Rozan LM, El-Deiry WS. p53 downstream target genes and tumor suppression: a classical view in evolution. Cell Death Differ. 2007;14(1):3–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991;253(5015):49–53.PubMedCrossRefGoogle Scholar
  7. 7.
    Niedobitek G, Agathanggelou A, Barber P, Smallman LA, Jones EL, Young LS. P53 overexpression and Epstein-Barr virus infection in undifferentiated and squamous cell nasopharyngeal carcinomas. J Pathol. 1993;170(4):457–61.PubMedCrossRefGoogle Scholar
  8. 8.
    Sheu LF, Chen A, Tseng HH, Leu FJ, Lin JK, Ho KC, et al. Assessment of p53 expression in nasopharyngeal carcinoma. Hum Pathol. 1995;26(4):380–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Ara S, Lee PS, Hansen MF, Saya H. Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res. 1990;18(16):4961.PubMedCrossRefGoogle Scholar
  10. 10.
    Hadhri-Guiga B, Toumi N, Khabir A, Sellami-Boudawara T, Ghorbel A, Daoud J, et al. Proline homozygosity in codon 72 of TP53 is a factor of susceptibility to nasopharyngeal carcinoma in Tunisia. Cancer Genet Cytogenet. 2007;178(2):89–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Jiang P, Liu J, Zeng X, Li W, Tang J. Association of TP53 codon 72 polymorphism with cervical cancer risk in Chinese women. Cancer Genet Cytogenet. 2010;197(2):174–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Gao LB, Li LJ, Pan XM, Li ZH, Liang WB, Bai P, et al. A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer. Biol Chem. 2013;394(3):415–20.PubMedCrossRefGoogle Scholar
  13. 13.
    Denisov EV, Cherdyntseva NV, Litvyakov NV, Slonimskaya EM, Malinovskaya EA, Voevoda MI, et al. TP53 mutations and Arg72Pro polymorphism in breast cancers. Cancer Genet Cytogenet. 2009;192(2):93–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Fernandez-Rubio A, Lopez-Cima MF, Gonzalez-Arriaga P, Garcia-Castro L, Pascual T, Marron MG, et al. The TP53 Arg72Pro polymorphism and lung cancer risk in a population of Northern Spain. Lung Cancer. 2008;61(3):309–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Chen HC, Chen GH, Chen YH, Liao WL, Liu CY, Chang KP, et al. MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer. 2009;100(6):1002–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Luo Z, Zhang L, Li Z, Li X, Li G, Yu H, et al. An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma. BMC Med Genomics. 2012;5:3.PubMedCrossRefGoogle Scholar
  17. 17.
    Li T, Chen JX, Fu XP, Yang S, Zhang Z, Chen KH, et al. microRNA expression profiling of nasopharyngeal carcinoma. Oncol Rep. 2011;25(5):1353–63.PubMedGoogle Scholar
  18. 18.
    Xu Y, Liu L, Liu J, Zhang Y, Zhu J, Chen J, et al. A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma. Int J Cancer. 2011;128(2):412–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Bossard P, Zaret KS. GATA transcription factors as potentiators of gut endoderm differentiation. Development. 1998;125(24):4909–17.PubMedGoogle Scholar
  20. 20.
    Chou J, Provot S, Werb Z. GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol. 2010;222(1):42–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Li L, Sima X, Bai P, Zhang L, Sun H, Liang W, et al. Interactions of miR-34b/c and TP53 polymorphisms on the risk of intracranial aneurysm. Clin Dev Immunol. 2012;2012:567–86.Google Scholar
  22. 22.
    Calin GA, Sevignani C, Dan Dumitru C, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. P Natl Acad Sci USA. 2004;101(9):2999–3004.CrossRefGoogle Scholar
  23. 23.
    Sevignani C, Calin GA, Nnadi SC, Shimizu M, Davuluri RV, Hyslop T, et al. MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci U S A. 2007;104(19):8017–22.PubMedCrossRefGoogle Scholar
  24. 24.
    Calin GA, Croce CM. Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. J Clin Invest. 2007;117(8):2059–66.PubMedCrossRefGoogle Scholar
  25. 25.
    Suzuki H, Toyota M, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68(11):4123–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Lee CH, Subramanian S, Beck AH, Espinosa I, Senz J, Zhu SX, et al. MicroRNA profiling of BRCA1/2 mutation-carrying and non-mutation-carrying high-grade serous carcinomas of ovary. PLoS One. 2009;4(10):e7314.Google Scholar
  27. 27.
    He C, Xiong J, Xu X, Lu W, Liu L, Xiao D, et al. Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun. 2009;388(1):35–40.PubMedCrossRefGoogle Scholar
  28. 28.
    Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 2008;105(36):13556–61.PubMedCrossRefGoogle Scholar
  29. 29.
    Corney DC, Hwang CI, Matoso A, Vogt M, Flesken-Nikitin A, Godwin AK, et al. Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res. 2010;16(4):1119–28.PubMedCrossRefGoogle Scholar
  30. 30.
    Kim NH, Kim HS, Kim NG, Lee I, Choi HS, Li XY, et al. p53 and microRNA-34 are suppressors of canonical Wnt signaling. Sci Signal. 2011;4(197):ra71.PubMedCrossRefGoogle Scholar
  31. 31.
    Wei YG, Liu F, Li B, Chen X, Ma Y, Yan LN, et al. Interleukin-10 gene polymorphisms and hepatocellular carcinoma susceptibility: a meta-analysis. World J Gastroenterol. 2011;17(34):3941–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhang YM, Zhou XC, Xu Z, Tang CJ. Meta-analysis of epidemiological studies of association of two polymorphisms in the interleukin-10 gene promoter and colorectal cancer risk. Genet Mol Res. 2012;11(3):3389–97.PubMedCrossRefGoogle Scholar
  33. 33.
    Tsai MH, Lin CD, Hsieh YY, Chang FC, Tsai FJ, Chen WC, et al. Prognostic significance of the proline form of p53 codon 72 polymorphism in nasopharyngeal carcinoma. Laryngoscope. 2002;112(1):116–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Tiwawech D, Srivatanakul P, Karaluk A, Ishida T. The p53 codon 72 polymorphism in Thai nasopharyngeal carcinoma. Cancer Lett. 2003;198(1):69–75.PubMedCrossRefGoogle Scholar
  35. 35.
    Birgander R, Sjalander A, Zhou Z, Fan C, Beckman L, Beckman G. p53 polymorphisms and haplotypes in nasopharyngeal cancer. Hum Hered. 1996;46(1):49–54.PubMedCrossRefGoogle Scholar
  36. 36.
    Yung WC, Ng MH, Sham JS, Choy DT. p53 codon 72 polymorphism in nasopharyngeal carcinoma. Cancer Genet Cytogenet. 1997;93(2):181–2.PubMedCrossRefGoogle Scholar
  37. 37.
    Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010;17(2):193–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Bale SJ, Dracopoli NC, Tucker MA, Clark Jr WH, Fraser MC, Stanger BZ, et al. Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p. N Engl J Med. 1989;320(21):1367–72.PubMedCrossRefGoogle Scholar
  39. 39.
    Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Korner H, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 2008;7(16):2591–600.PubMedCrossRefGoogle Scholar
  40. 40.
    Tanaka K, Yanoshita R, Konishi M, Oshimura M, Maeda Y, Mori T, et al. Suppression of tumourigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region. Oncogene. 1993;8(8):2253–8.PubMedGoogle Scholar
  41. 41.
    Attiyeh EF, London WB, Mosse YP, Wang Q, Winter C, Khazi D, et al. Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med. 2005;353(21):2243–53.PubMedCrossRefGoogle Scholar
  42. 42.
    Cohen SM, Brennecke J, Stark A. Denoising feedback loops by thresholding—a new role for microRNAs. Genes Dev. 2006;20(20):2769–72.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of Forensic Biology, West China School of Preclinical and Forensic MedicineSichuan UniversityChengduPeople’s Republic of China
  2. 2.Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University HospitalSichuan UniversityChengduPeople’s Republic of China
  3. 3.Department of Head and Neck OncologyChongqing Cancer HospitalChongqingPeople’s Republic of China
  4. 4.Department of Neurosurgery, West China HospitalSichuan UniversityChengduPeople’s Republic of China
  5. 5.Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth DefectsMinistry of EducationChengduPeople’s Republic of China

Personalised recommendations