Skip to main content
Log in

Association between circulating interleukin-1 beta (IL-1β) levels and IL-1β C–511T polymorphism with cervical cancer risk in Egyptian women

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cancer cervix is one of the leading causes of cancer-related mortality among women worldwide. It is believed that the host genetic factors such as inflammation-induced cytokines may play a role in cervical carcinogenesis. The interleukin-1β (IL-1β) gene contains several single nucleotide polymorphisms. One of them, C–511T, which in the promoter region has been associated with increased IL-1β production and with increased risk of developing cancers. We assessed the association between the IL-1β C–511T polymorphism and cervical cancer risk in a case–control study among 100 histopathologically confirmed Egyptian women with cervical cancer and 50 age-matched, cervical cytology negative, healthy controls by polymerase chain reaction-restriction fragment length polymorphism. Plasma levels of IL-1β were assayed by enzyme-linked immunosorbent assay. There was significant increase in the mean plasma IL-1β level in cervical cancer cases (43.40 ± 25.95 pg/ml) when compared with controls (30.51 ± 18.28 pg/ml, P = 0.002). The plasma levels above the 75th percentile of controls (IL-1β ≥ 45.74 pg/ml) were significantly associated with a 2.49-fold increased risk of cervical cancer. The significant increase in IL-1β concentration in cervical cancer cases was observed only among cervical cancer cases carrying C–511T variant genotypes. T/T genotype of IL-1β polymorphism was significantly higher in cervical cancer cases compared with controls (57 vs. 38%; OR = 2.16; P = 0.028) and the T allele carriage was significantly associated with cervical cancer risk (OR = 2.00, 95% CI = 1.19–3.38, and P = 0.008). In conclusion, plasma IL-1β level and IL-1β C–511T polymorphism may be considered as candidate biomarkers for cervical cancer in Egyptian women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156

    Article  PubMed  CAS  Google Scholar 

  2. Wallin KL, Wiklund F, Angstrom T, Bergman F, Stendahl U, Wadell G, Hallmans G, Dillner J (1999) Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer. N Engl J Med 341:1633–1638

    Article  PubMed  CAS  Google Scholar 

  3. zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350

    Article  PubMed  CAS  Google Scholar 

  4. Kang S, Kim JW, Park NH, Song YS, Park YP, Kang SB, Lee HP (2007) Interleukin-1Beta–511 polymorphism and risk of cervical cancer. J Korean Med Sci 22:110–113

    Article  PubMed  CAS  Google Scholar 

  5. Singh H, Sachan R, Goel H, Mittal B (2008) Genetic variants of interleukin-1RN and interleukin-1b genes and risk of cervical cancer. BJOG 115:633–638

    Article  PubMed  CAS  Google Scholar 

  6. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  7. Castle PE, Hillier SL, Rabe LK, Hildesheim A, Herrero R, Bratti MC, Sherman ME, Burk RD, Rodriguez AC, Alfaro M, Hutchinson ML, Morales J, Schiffman M (2001) An association of cervical inflammation with high-grade cervical neoplasia in women infected with oncogenic human papillomavirus (HPV). Cancer Epidemiol Biomarkers Prev 10:1021–1027

    PubMed  CAS  Google Scholar 

  8. Smith JS, Herrero R, Bosetti C, Munoz N, Bosch FX, Eluf-Neto J, Castellsague X, Meijer CJ, Van den Brule AJ, Franceschi S, Ashley R (2002) Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst 94:1604–1613

    PubMed  CAS  Google Scholar 

  9. Schwebke JR, Zajackowski ME (1997) Effect of concurrent lower genital tract infections on cervical cancer screening. Genitourin Med 73:383–386

    PubMed  CAS  Google Scholar 

  10. Bird S, Zou J, Wang T, Munday B, Cunningham C, Secombes CJ (2002) Evolution of interleukin-1beta. Cytokine Growth Factor Rev 13:483–502

    Article  PubMed  CAS  Google Scholar 

  11. Sehouli J, Mustea A, Koensgen D, Chen FCK, Lichtenegger W (2003) Interleukin-1 receptor antagonist gene polymorphism is associated with increased risk of epithelial ovarian cancer. Ann Oncol 14:1501–1504

    Article  PubMed  CAS  Google Scholar 

  12. Sobti RC, Kordi Tamandani DM, Shekari M, Kaur P, Malekzadeh K, Suri V (2008) Interleukin 1 beta gene polymorphism and risk of cervical cancer. Int J Gynaecol Obstet 101:47–52

    PubMed  CAS  Google Scholar 

  13. Smith DE, Renshaw BR, Ketchem RR, Garka KE, Sims JE (2000) Four new members expand the interleukin-1 superfamily. J Biol Chem 275:1169–1175

    Article  PubMed  CAS  Google Scholar 

  14. di Giovine FS, Takhsh S, Blakemore AI, Duff GW (1992) Single base polymorphism at–511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1:450–453

    Article  PubMed  Google Scholar 

  15. Gore EA, Sanders JJ, Pandey JP, Palesch Y, Galbraith GM (1998) Interleukin-1beta +3953 allele 2: Association with disease status in adult periodontitis. J Clin Periodontol 25:781–785

    Article  PubMed  CAS  Google Scholar 

  16. Hall SK, Perregaux DG, Gabel CA, Woodworth T, Durham LK, Huizinga TW, Breedveld FC, Seymour AB (2004) Correlation of polymorphic variation in the promoter region of the interleukin-1 beta gene with secretion of interleukin-1 beta protein. Arthritis Rheum 50:1976–1983

    Article  PubMed  CAS  Google Scholar 

  17. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF Jr, Rabkin CS (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398–402

    Article  PubMed  CAS  Google Scholar 

  18. Lee KA, Ki CS, Kim HJ, Sohn KM, Kim JW, Kang WK, Rhee JC, Song SY, Sohn TS (2004) Novel interleukin 1 beta polymorphism increased the risk of gastric cancer in a Korean population. J Gastroenterol 39:429–433

    Article  PubMed  CAS  Google Scholar 

  19. Liu J, Zhai X, Jin G, Hu Z, Wang S, Wang X, Qin J, Gao J, Ma H, Wang X, Wei Q, Shen H (2006) Functional variants in the promoter of interleukin-1beta are associated with an increased risk of breast cancer: a case–control analysis in a Chinese population. Int J Cancer 118:2554–2558

    Google Scholar 

  20. Zienolddiny S, Ryberg D, Maggini V, Skaug V, Canzian F, Haugen A (2004) Polymorphisms of the interleukin-1beta gene are associated with increased risk of non-small cell lung cancer. Int J Cancer 109:353–356

    Article  PubMed  CAS  Google Scholar 

  21. Achyut BR, Srivastava A, Bhattacharya S, Mittal B (2007) Genetic association of interleukin-1beta (-511C/T) and interleukin-1 receptor antagonist (86 bp repeat) polymorphisms with Type 2 diabetes mellitus in North Indians. Clin Chim Acta 377:163–169

    Google Scholar 

  22. Qian N, Chen X, Han S, Qiang F, Jin G, Zhou X, Dong J, Wang X, Shen H, Hu X (2010) Circulating IL-1β levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women. J Cancer Res Clin Oncol 136:709–716

    Article  PubMed  CAS  Google Scholar 

  23. Tjiong MY, van der Vange N, ter Schegget JS, Burger MP, ten Kate FW, Out TA (2001) Cytokines in cervicovaginal washing fluid from patients with cervical neoplasia. Cytokine 14:357–360

    Google Scholar 

  24. Behbakht K, Friedman J, Heimler I, Aroutcheva A, Simoes J, Faro S (2002) Role of the vaginal microbiological ecosystem and cytokine profile in the promotion of cervical dysplasia: a case-control study. Infect Dis Obstet Gynecol 10:181–186

    Article  PubMed  Google Scholar 

  25. Majeed GS, Glew S, Bidwell J (1999) An association between LSIL and the high secretor phenotype of IL-1beta. Gynecol Oncol 73:359–361

    Article  PubMed  CAS  Google Scholar 

  26. Stanczuk GA, Sibanda EN, Perrey C, Chirara M, Pravica V, Hutchinson IV, Tswana SA (2001) Cancer of the uterine cervix may be significantly associated with a gene polymorphism coding for increased IL-10 production. Int J Cancer 94:792–794

    Article  PubMed  CAS  Google Scholar 

  27. Deshpande A, Nolan JP, White PS, Valdez YE, Hunt WC, Peyton CL, Wheeler CM (2005) TNF-alpha promoter polymorphisms and susceptibility to human papillomavirus 16-associated cervical cancer. J Infect Dis 191:969–976

    Article  PubMed  CAS  Google Scholar 

  28. Thomas M, Pim D, Banks L (1999) The role of the E6–p53 interaction in the molecular pathogenesis of HPV. Oncogene 18:7690–7700

    Article  PubMed  CAS  Google Scholar 

  29. Fu L, Van Doorslaer K, Chen Z, Ristriani T, Masson M, Travé G, Burk RD (2010) Degradation of p53 by human alpha papillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity. PLoS ONE 5(9):e12816. doi:10.1371/journal.pone.0012816

    Article  PubMed  Google Scholar 

  30. Asschert JG, Vellenga E, Hollema H, van der Zee AG, de Vries EG (1997) Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), interleukin-11 (IL-11) and tumour necrosis factor-alpha (TNF-alpha) in p53-characterised human ovarian carcinomas. Eur J Cancer 33:2246–2251

    Article  PubMed  CAS  Google Scholar 

  31. Hybertson BM, Lee YM, Cho HG, Cho OJ, Repine JE (2000) Alveolar type II cell abnormalities and peroxide formation in lungs of rats given IL-1 intratracheally. Inflammation 24:289–293

    Article  PubMed  CAS  Google Scholar 

  32. Jaiswal M, LaRusso NF, Burgart LJ, Gores GJ (2000) Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res 60:184–190

    PubMed  CAS  Google Scholar 

  33. Simonart T, Van Vooren JP (2002) Interleukin-1beta increases the BCL- 2/BAX ratio in Kaposi’s sarcoma cells. Cytokine 19:259–266

    Article  PubMed  CAS  Google Scholar 

  34. Hirankarn N, Kimkong I, Kummee P, Tangkijvanich P, Poovorawan Y (2006) Interleukin-1beta gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection. World J Gastroenterol 12:776–779

    PubMed  CAS  Google Scholar 

  35. Chang YW, Jang JY, Kim NH, Lee JW, Lee HJ, Jung WW, Dong SH, Kim HJ, Kim HB, Lee JI, Chang R (2005) Interleukin-1β (IL-1β) polymorphisms and gastric mucosal levels of IL-1beta cytokine in Korean patients with gastric cancer. Int J Cancer 114:465–471

    Article  PubMed  CAS  Google Scholar 

  36. Chen H, Wilkins LM, Aziz N, Cannings C, Wyllie DH, Bingle C, Rogus J, Beck JD, Offenbacher S, Cork MJ, Rafie-Kolpin M, Hsieh CM, Kornman KS, Duff GW (2006) Single nucleotide polymorphisms in the human interleukin-1β gene affect transcription according to haplotype context. Hum Mol Genet 15:519–529

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors are grateful to Dr Bahaa ElDin Hasan for his skilled technical assistance.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rasha L. Etewa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Al-Tahhan, M.A., Etewa, R.L. & El Behery, M.M. Association between circulating interleukin-1 beta (IL-1β) levels and IL-1β C–511T polymorphism with cervical cancer risk in Egyptian women. Mol Cell Biochem 353, 159–165 (2011). https://doi.org/10.1007/s11010-011-0782-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-0782-9

Keywords

Navigation