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Tumor Biology

, Volume 35, Issue 12, pp 12275–12284 | Cite as

Effects of interleukin-18 promoter (C607A and G137C) gene polymorphisms and their association with oral squamous cell carcinoma (OSCC) in northern India

  • Prithvi Kumar Singh
  • Mohd. Kaleem Ahmad
  • Vijay Kumar
  • Syed Rizwan Hussain
  • Rajni Gupta
  • Amita Jain
  • Abbas Ali Mahdi
  • Jaishri Bogra
  • Girish ChandraEmail author
Research Article

Abstract

Interleukin-18 (IL-18) is one of the immunomodulatory cytokines that plays an important role in cellular functions against tumor development and progression. IL-18 (-607) C/A and (-0137) G/C gene promoter polymorphisms and their haplotypes variants are associated with risk of various cancers. We evaluated a possible association of IL-18 (-607) C/A and (-137) G/C gene promoter polymorphisms in the susceptibility to oral squamous cell carcinoma (OSCC). A total number of 272 patients with OSCC and 185 healthy volunteers were genotyped for the IL-18 (-607) C/A and (-137) G/C polymorphism. Polymorphism variants were examined by using tetra-primer amplification refractory mutation system (T-ARMS). Genotype frequencies were evaluated by chi-square test and odds ratio (OR) relative risk. IL-18 (-137) G/C gene polymorphism was significantly associated with the risk of OSCC as compared to healthy volunteers (genotype GG vs GC: OR 2.238; 95 % CI 1.455-3.441; p = 0.0003 and allele G vs C: OR 1.984; 95 % CI 1.335–2.947; p = 0.0007). The genotype and allele frequencies of the IL-18 promoter -607 C/A polymorphism in OSCC patients were not significantly different than that in healthy controls (p > 0.05). Our results suggest that IL-18 -137 G/C polymorphism is significantly associated with the progression of oral cancer but -607 C/A polymorphism is not associated with this.

Keywords

Oral squamous cell carcinoma Cytokines Interleukin Inflammation Genotype 

Notes

Acknowledgments

This work was financially supported by a grant from Indian Council of Medical Research (ICMR).

Conflicts of interest

None

References

  1. 1.
    World Health Organization. Strengthening the prevention of oral cancer: the WHO perspective. http://www.who.int/oral_health/publications/CDOE05_vol33_397_9/en/ (accessed on 26 Oct 2013)
  2. 2.
    International Agency for Research on Cancer. GLOBOCAN 2008. http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900 (accessed on 26 Oct 2013)
  3. 3.
    Williams HK. Molecular pathogenesis of oral carcinoma. J Clin Pathol. 2000;53:165–72.CrossRefGoogle Scholar
  4. 4.
    Martone T, Bellone G, Pagano M, Beatrice F, Palonta F, et al. Constitutive expression of interleukin-18 in head and neck squamous carcinoma cells. Head Neck. 2004;26:494–503.PubMedCrossRefGoogle Scholar
  5. 5.
    Srivastava S, Salim N, Robertson MJ. Interleukin-18: biology and role in the immunotherapy of cancer. Curr Med Chem. 2010;17:3353–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Nilkaeo A, Bhuvanath S. Role of interleukin-18 in modulation of oral carcinoma cell proliferation. Mediat Inflamm. 2006;3:67120.Google Scholar
  7. 7.
    Liu W, Han B, Sun B, Gao Y, Huang Y, et al. Overexpression of interleukin-18 induces growth inhibition, apoptosis and gene expression changes in a human tongue squamous cell carcinoma cell line. J Int Med Res. 2012;40:537–44.PubMedCrossRefGoogle Scholar
  8. 8.
    Park S, Cheon S, Cho D. The dual effects of interleukin-18 in tumor progression. Cell Mol Immunol. 2007;4:329–35.PubMedGoogle Scholar
  9. 9.
    Giedraitis V, He B, Huang WX, Hillert J. Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J Neuroimmunol. 2001;112:146–52.PubMedCrossRefGoogle Scholar
  10. 10.
    Loyha K, Vatanasapt P, Promthet S, Parkin DM. Risk factors for oral cancer in northeast Thailand. Asian Pac J Cancer Prev. 2012;13:5087–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Ray JG, Ganguly M, Rao BS, Mukherjee S, Mahato B, et al. Clinico-epidemiological profile of oral potentially malignant and malignant conditions among areca nut, tobacco and alcohol users in Eastern India: a hospital based study. J Oral Maxillofac Pathol. 2013;17:45–50.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Gupta B, Ariyawardana A, Johnson NW. Oral cancer in India continues in epidemic proportions: evidence base and policy initiatives. Int Dent J. 2013;63:12–25.PubMedCrossRefGoogle Scholar
  13. 13.
    Tsai H-T, Hsin C-H, Hsieh Y-H, Tang C-H, Yang S-F, et al. Impact of interleukin-18 polymorphisms -607A/C and -137G/C on oral cancer occurrence and clinical progression. PLoS One. 2013;8(12):e83572. doi: 10.1371/journal.pone.0083572.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Teng YH, Liu TH, Tseng HC, Chung TT, Yeh CM, et al. Contribution of genetic polymorphisms of stromal cell-derived factor-1 and its receptor, CXCR4, to the susceptibility and clinicopathologic development of oral cancer. Head Neck. 2009;31:1282–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Chen MK, Chiou HL, Su SC, Chung TT, Tseng HC, et al. The association between hypoxia inducible factor-1alpha gene polymorphisms and increased susceptibility to oral cancer. Oral Oncol. 2009;45:e222–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Chen MK, Tsai HT, Chung TT, Su SC, Kao TY, et al. Glutathione S-transferase P1 and alpha gene variants; role in susceptibility and tumor size development of oral cancer. Head Neck. 2010;32:1079–87.PubMedCrossRefGoogle Scholar
  17. 17.
    Wei YS, Lan Y, Liu YG, Tang H, Tang RG, Wang JC. Interleukin-18 gene promoter polymorphisms and the risk of esophageal squamous cell carcinoma. Acta Oncol. 2007;46:10906.CrossRefGoogle Scholar
  18. 18.
    Liu Y, Lin N, Huang L, Xu Q, Pang G. Genetic polymorphisms of the interleukin-18 gene and risk of prostate cancer. DNA Cell Biol. 2007;26:6138.Google Scholar
  19. 19.
    Nikiteas N, Yannopoulos A, Chatzitheofylaktou A, Tsigris C. Heterozygosity for interleukin-18 -607 A/C polymorphism is associated with risk for colorectal cancer. Anticancer Res. 2007;27:384953.Google Scholar
  20. 20.
    Bushley AW, Ferrell R, McDuffie K, Terada KY, Carney ME, Thompson PJ, et al. Polymorphisms of interleukin [IL]- 1alpha, IL-1beta, IL-6, IL-10, and IL-18 and the risk of ovarian cancer. Gynecol Oncol. 2004;95:6729.CrossRefGoogle Scholar
  21. 21.
    Vairaktaris E, Serefoglou ZC, Yapijakis C, Agapi C, Vassiliou S, Nkenke E, et al. The interleukin-18 -607A/C polymorphism is not associated with risk for oral cancer. Anticancer Res. 2007;27:4011–4.PubMedGoogle Scholar
  22. 22.
    Asefi V, Mojtahedi Z, Khademi B, Naeimi S, Ghaderi A. Head and neck squamous cell carcinoma (HNSCC) is not associated with interleukin-18 promoter gene polymorphisms, a case control study. J Laryngol Otol. 2009;123:4448.CrossRefGoogle Scholar
  23. 23.
    Khalili-Azad T, Razmkhah M, Ghiam AF, Doroudchi M, Talei AR, Mojtahedi Z, et al. Association of interleukin-18 gene promoter polymorphisms with breast cancer. Neoplasma. 2009;56:225.CrossRefGoogle Scholar
  24. 24.
    Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Taheri M, Hashemi-Shahri SM, Hamzehnejadi M, Naderi M, Moazeni-Roodi A, Bahari G, et al. Lack of association between interleukin-18 -607 C/A gene polymorphism and pulmonary tuberculosis in Zahedan, southeast Iran. Prauge Med Rep. 2012;113:16–22.Google Scholar
  26. 26.
    Haghshenas MR, Hosseini SV, Mahmoudi M, Saberi-Firozi M, Farjadian S, Ghaderi A. IL-18 serum level and IL-18 promoter gene polymorphism in Iranian patients with gastrointestinal cancers. J Gastroenterol Hepatol. 2009;24:1119–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 2001;12:53–72.PubMedCrossRefGoogle Scholar
  28. 28.
    Kim KE, Song H, Kim TS, et al. Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines. Oncogene. 2007;26:1468–76.PubMedCrossRefGoogle Scholar
  29. 29.
    Mojtahedi Z. Interleukin (IL)-18 may enhance Th1 response in early cancer but aggravate malignant disease in its later stages. Med Hypotheses. 2005;65:995–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol. 2006;72:1605–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Vidal-Vanaclocha F, Mendoza L, Telleria N, Salado C, Valcárcel M, Gallot N, et al. Clinical and experimental approaches to the pathophysiology of interleukin-18 in cancer progression. Cancer Metastasis Rev. 2006;25:417–34.PubMedCrossRefGoogle Scholar
  32. 32.
    Lian H, Jin N, Li X, Mi Z, Zhang J, Sun L, et al. Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and apoptin. Cancer Immunol Immunother. 2007;56:181–92.PubMedCrossRefGoogle Scholar
  33. 33.
    Herzyk DJ, Bugelski PJ, Hart TK, Wier PJ. Preclinical safety of recombinant human interleukin-18. Toxicol Pathol. 2003;31:554–61.PubMedCrossRefGoogle Scholar
  34. 34.
    Lebel-Binay S, Thiounn N, De Pinieux G, Viellefond A, Debré B, Bonnefoy JY, et al. IL-18 is produced by prostate cancer cells and secreted in response to interferons. Int J Cancer. 2003;106:827–35.PubMedCrossRefGoogle Scholar
  35. 35.
    Riedel F, Adam S, Feick P, Haas S, Götte K, Hörmann K. Expression of IL-18 in patients with head and neck squamous cell carcinoma. Int J Mol Med. 2004;13:267–72.PubMedGoogle Scholar
  36. 36.
    Lissoni P, Brivio F, Rovelli F, Fumagalli G, Malugani F, Vaghi M, et al. Serum concentrations of interleukin-18 in early and advanced cancer patients: enhanced secretion in metastatic disease. J Boil Regul Homoest Agents. 2000;14:275–7.Google Scholar
  37. 37.
    Cao R, Farnebo J, Kurimoto M, Cao Y. Interleukin-18 acts as an angiogenesis and tumor suppressor. FASEB. 1999;13:2195–202.Google Scholar
  38. 38.
    Golab J. Interleukin-18-interferon Á inducing factor- · novel player in tumor immunotherapy? Cytokine. 2000;12:332–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Wang ZY, Gaggero A, Rubartelli A, Rosso O, Miotti S, Mizzanzanica D, et al. Expression of interleukin-18 in human ovarian carcinoma and normal ovarian epithelium: evidence for defective processing in tumor cells. In J Cancer. 2002;98:873–8.Google Scholar
  40. 40.
    Nilkaeo A, Bhuvanath S. Role of interleukin-18 in modulation of oral carcinoma cell proliferation. Mediat Inflamm. 2006;3:1–6.CrossRefGoogle Scholar
  41. 41.
    Farjadfar A, Mojtahedi Z, Ghayumi MA. Interleukin-18 promoter polymorphism is associated with lung cancer: a case–control study. Acta Oncol. 2009;48:971–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Sobti RC, Shekari M, Tamandani DM, Malekzadeh K, Suri V. Association of interleukin-18 gene promoter polymorphismon the risk of cervix carcinogenesis in North Indian population. Oncol Res. 2008;17:159–66.PubMedCrossRefGoogle Scholar
  43. 43.
    Jaiswal PK, Singh V, Srivastava P, Mittal RD. Association of IL-12, IL-18 variants and serum IL-18 with bladder cancer susceptibility in North Indian population. Gene. 2013;519:128–34.PubMedCrossRefGoogle Scholar
  44. 44.
    Sáenz-López P et al. Impact of interleukin-18 polymorphisms -607 and -137 on clinical characteristics of renal cell carcinoma patients. Hum Immunol. 2010;71:309–13.PubMedCrossRefGoogle Scholar
  45. 45.
    Farhat K, Hassen E, Bouzgarrou N, Gabbouj S, Bouaouina N, Chouchane L. Functional IL-18 promoter gene polymorphisms in Tunisian nasopharyngeal carcinoma patients. Cytokine. 2008;43:132–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Naeimi S, Ghiam AF, Mojtahedi Z, Dehaghani AS, Amani D, Ghaderi A. Interleukin-18 gene promoter polymorphisms and recurrent spontaneous abortion. Eur J Obstet Gynecol Reprod Biol. 2006;128:5–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Nikiteas N, Yannopoulos A, Chatzitheofylaktou A, Tsigris C. Heterozygosity for interleukin-18 -607A/C polymorphism is associated with risk for colorectal cancer. Anticancer Res. 2007;27:3849–53.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Prithvi Kumar Singh
    • 1
  • Mohd. Kaleem Ahmad
    • 2
  • Vijay Kumar
    • 3
  • Syed Rizwan Hussain
    • 2
  • Rajni Gupta
    • 1
  • Amita Jain
    • 4
  • Abbas Ali Mahdi
    • 2
  • Jaishri Bogra
    • 1
  • Girish Chandra
    • 1
    Email author
  1. 1.Department of AnaesthesiologyKing George’s Medical UniversityLucknowIndia
  2. 2.Department of BiochemistryKing George’s Medical UniversityLucknowIndia
  3. 3.Department of Surgical OncologyKing George’s Medical UniversityLucknowIndia
  4. 4.Department of MicrobiologyKing George’s Medical UniversityLucknowIndia

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