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Genetic polymorphisms of interleukin-1 beta and osteosarcoma risk

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Abstract

Purpose

Osteosarcoma is the most common childhood bone cancer. Interleukin-1 beta (IL-1B) is crucially involved in osteosarcoma carcinogenesis. Whether genetic polymorphisms of IL-1B also influence osteosarcoma risk is unknown. The aim of this study was to investigate the association between IL-1B gene polymorphisms and osteosarcoma risk in Chinese Han patients.

Methods

A hospital-based case–control study involving 120 osteosarcoma patients and 120 controls was conducted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect three IL-1B gene polymorphisms (−31 T/C, −511 C/T and +3954 C/T) in these patients.

Results

Patients with osteosarcoma had a significantly lower frequency of −31 CC genotype [odds ratio (OR) = 0.40, 95 % confidence interval (CI) = 0.17–0.92; P = 0.03] and −31 C allele (OR = 0.67, 95 % CI = 0.46–0.99; P = 0.04) than controls. Patients with osteosarcoma had a significantly lower frequency of −511 TT genotype (OR = 0.40, 95 % CI = 0.17–0.95; P = 0.04) than controls. The +3954 C/T gene polymorphisms were not associated with a risk of osteosarcoma. When stratified by Enneking stage, tumour location, histological type, tumour metastasis of osteosarcoma and family history of cancer, no statistically significant results were found.

Conclusions

This is the first study to provide evidence for an association of IL-1B gene polymorphisms with osteosarcoma risk.

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Abbreviations

IL-1B:

Interleukin-1 beta

PCR-RFLP:

Polymerase chain reaction restriction fragment length polymorphism

OR:

Odds ratio

CI:

Confidence interval

SNPs:

Single-nucleotide polymorphisms

UTR:

Untranslated region

NSCLC:

Non-small-cell lung cancer

References

  1. Mirabello L, Troisi RJ, Savage SA (2009) Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer 115:1531–1543

    Article  PubMed Central  PubMed  Google Scholar 

  2. Ottaviani G, Jaffe N (2009) The epidemiology of osteosarcoma. Cancer Treat Res 152:3–13

    Article  PubMed  Google Scholar 

  3. Powers M, Zhang W, Lopez-Terrada D et al (2010) The molecular pathology of sarcomas. Cancer Biomark 9:475–491

    PubMed  Google Scholar 

  4. Bovee JV, Hogendoorn PC (2010) Molecular pathology of sarcomas: concepts and clinical implications. Virchows Arch 456:193–199

    Article  PubMed Central  PubMed  Google Scholar 

  5. de Alava E (2007) Molecular pathology in sarcomas. Clin Transl Oncol 9:130–144

    Article  PubMed  Google Scholar 

  6. Osuna D, de Alava E (2009) Molecular pathology of sarcomas. Rev Recent Clin Trials 4:12–26

    Article  CAS  PubMed  Google Scholar 

  7. Berger M, Muraro M, Fagioli F et al (2008) Osteosarcoma derived from donor stem cells carrying the Norrie’s disease gene. N Engl J Med 359:2502–2504

    Article  CAS  PubMed  Google Scholar 

  8. Romeo S, Dei Tos AP (2011) Clinical application of molecular pathology in sarcomas. Curr Opin Oncol 23:379–384

    Article  CAS  PubMed  Google Scholar 

  9. He M, Wang Z, Zhao J et al (2014) COL1A1 polymorphism is associated with risks of osteosarcoma susceptibility and death. Tumour Biol 35:1297–1305

    Article  CAS  PubMed  Google Scholar 

  10. He ML, Wu Y, Zhao JM et al (2013) PIK3CA and AKT gene polymorphisms in susceptibility to osteosarcoma in a Chinese population. Asian Pac J Cancer Prev 14:5117–5122

    Article  PubMed  Google Scholar 

  11. Jia J, Tian Q, Liu Y et al (2013) Interactive effect of bisphenol A (BPA) exposure with -22G/C polymorphism in LOX gene on the risk of osteosarcoma. Asian Pac J Cancer Prev 14:3805–3808

    Article  PubMed  Google Scholar 

  12. Zhang SL, Mao NF, Sun JY et al (2012) Predictive potential of glutathione S-transferase polymorphisms for prognosis of osteosarcoma patients on chemotherapy. Asian Pac J Cancer Prev 13:2705–2709

    Article  PubMed  Google Scholar 

  13. Wang W, Wang J, Song H et al (2011) Cytotoxic T-lymphocyte antigen-4 + 49G/A polymorphism is associated with increased risk of osteosarcoma. Genet Test Mol Biomark 15:503–506

    Article  CAS  Google Scholar 

  14. Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147

    CAS  PubMed  Google Scholar 

  15. El-Omar EM, Carrington M, Chow WH et al (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398–402

    Article  CAS  PubMed  Google Scholar 

  16. El-Omar EM, Carrington M, Chow WH et al (2001) The role of interleukin-1 polymorphisms in the pathogenesis of gastric cancer. Nature 412:99

    Article  CAS  PubMed  Google Scholar 

  17. Dennis RA, Trappe TA, Simpson P et al (2004) Interleukin-1 polymorphisms are associated with the inflammatory response in human muscle to acute resistance exercise. J Physiol 560:617–626

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Vijgen L, Van Gysel M, Rector A et al (2002) Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease. Genes Immun 3:400–406

    Article  CAS  PubMed  Google Scholar 

  19. Nemetz A, Kope A, Molnar T et al (1999) Significant differences in the interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in a Hungarian population with inflammatory bowel disease. Scand J Gastroenterol 34:175–179

    Article  CAS  PubMed  Google Scholar 

  20. Heresbach D, Alizadeh M, Dabadie A et al (1997) Significance of interleukin-1beta and interleukin-1 receptor antagonist genetic polymorphism in inflammatory bowel diseases. Am J Gastroenterol 92:1164–1169

    CAS  PubMed  Google Scholar 

  21. Armour KJ, Smith NW, Brown BL et al (1995) Interleukin-1 beta induces the synthesis of adenylyl cyclase in Swiss 3T3 fibroblasts and MG-63 osteosarcoma cells. Biochem Biophys Res Commun 212:293–299

    Article  CAS  PubMed  Google Scholar 

  22. Dedhar S (1989) Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin-1 beta in human osteosarcoma cells: inhibition of cell proliferation and stimulation of alkaline phosphatase activity. J Cell Physiol 138:291–299

    Article  CAS  PubMed  Google Scholar 

  23. Dedhar S (1989) Signal transduction via the beta 1 integrins is a required intermediate in interleukin-1 beta induction of alkaline phosphatase activity in human osteosarcoma cells. Exp Cell Res 183:207–214

    Article  CAS  PubMed  Google Scholar 

  24. Yang W, He M, Zhao J et al (2014) Association of ITGA3 gene polymorphisms with susceptibility and clinicopathological characteristics of osteosarcoma. Med Oncol 31:826

    Article  PubMed  Google Scholar 

  25. Wang J, Nong L, Wei Y et al (2013) Association of interleukin-12 polymorphisms and serum IL-12p40 levels with osteosarcoma risk. DNA Cell Biol 32:605–610

    Article  PubMed  Google Scholar 

  26. Liu J, Wang J, Jiang W et al (2013) Effect of cytotoxic T-lymphocyte antigen-4, TNF-alpha polymorphisms on osteosarcoma: evidences from a meta-analysis. Chin J Cancer Res 25:671–678

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Liu Y, He Z, Feng D et al (2011) Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to osteosarcoma. DNA Cell Biol 30:1051–1055

    Article  CAS  PubMed  Google Scholar 

  28. He J, Wang J, Wang D et al (2013) Association analysis between genetic variants of MDM2 gene and osteosarcoma susceptibility in Chinese. Endocr J 60:1215–1220

    Article  CAS  PubMed  Google Scholar 

  29. Wang W, Song H, Liu J et al (2011) CD86 + 1057G/A polymorphism and susceptibility to osteosarcoma. DNA Cell Biol 30:925–929

    Article  CAS  PubMed  Google Scholar 

  30. Hu YS, Pan Y, Li WH et al (2011) Int7G24A variant of transforming growth factor-beta receptor 1 is associated with osteosarcoma susceptibility in a Chinese population. Med Oncol 28:622–625

    Article  CAS  PubMed  Google Scholar 

  31. Ergen A, Kilicoglu O, Ozger H et al (2011) Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma. Mol Biol Rep 38:4181–4184

    Article  CAS  PubMed  Google Scholar 

  32. Koshkina NV, Kleinerman ES, Li G et al (2007) Exploratory analysis of Fas gene polymorphisms in pediatric osteosarcoma patients. J Pediatr Hematol Oncol 29:815–821

    Article  CAS  PubMed  Google Scholar 

  33. He B, Zhang Y, Pan Y et al (2011) Interleukin 1 beta (IL1B) promoter polymorphism and cancer risk: evidence from 47 published studies. Mutagenesis 26:637–642

    Article  CAS  PubMed  Google Scholar 

  34. He BS, Pan YQ, Xu YF et al (2011) Polymorphisms in interleukin-1B (IL-1B) and interleukin 1 receptor antagonist (IL-1RN) genes associate with gastric cancer risk in the Chinese population. Dig Dis Sci 56:2017–2023

    Article  CAS  PubMed  Google Scholar 

  35. Wang P, Xia HH, Zhang JY et al (2007) Association of interleukin-1 gene polymorphisms with gastric cancer: a meta-analysis. Int J Cancer 120:552–562

    Article  CAS  PubMed  Google Scholar 

  36. Al-Tahhan MA, Etewa RL, El Behery MM (2011) Association between circulating interleukin-1 beta (IL-1beta) levels and IL-1beta C-511T polymorphism with cervical cancer risk in Egyptian women. Mol Cell Biochem 353:159–165

    Article  CAS  PubMed  Google Scholar 

  37. Sobti RC, Kordi Tamandani DM, Shekari M et al (2008) Interleukin 1 beta gene polymorphism and risk of cervical cancer. Int J Gynaecol Obstet 101:47–52

    Article  CAS  PubMed  Google Scholar 

  38. Wu KS, Zhou X, Zheng F et al (2010) Influence of interleukin-1 beta genetic polymorphism, smoking and alcohol drinking on the risk of non-small cell lung cancer. Clin Chim Acta 411:1441–1446

    Article  CAS  PubMed  Google Scholar 

  39. Barber MD, Powell JJ, Lynch SF et al (2000) A polymorphism of the interleukin-1 beta gene influences survival in pancreatic cancer. Br J Cancer 83:1443–1447

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

Thanks are expressed to all coinvestigators, local project coordinators, research assistants, laboratory technicians and secretaries/administrative assistants.

Competing interest

None.

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Authors

Corresponding authors

Correspondence to Hong Wang or ShuHua Yang.

Additional information

Yu He and Xinjun Liang contributed equally to this work and are joint first authors.

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He, Y., Liang, X., Meng, C. et al. Genetic polymorphisms of interleukin-1 beta and osteosarcoma risk. International Orthopaedics (SICOT) 38, 1671–1676 (2014). https://doi.org/10.1007/s00264-014-2374-2

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  • DOI: https://doi.org/10.1007/s00264-014-2374-2

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