Tumor Biology

, Volume 37, Issue 7, pp 9807–9811 | Cite as

Genetic variations in interleukin-6 polymorphism and the association with susceptibility and overall survival of osteosarcoma

  • Yunlong QiEmail author
  • Chengbin Zhao
  • Hongxi Li
  • Benning Zhang
  • Kazuhiro Tada
  • Hiroyuki Abe
  • Midori Tada
Original Article


Interleukin-6 (IL-6), a central proinflammatory cytokine, may be involved in both development and progression of many human malignancies. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms with susceptibility and overall survival of osteosarcoma in a Chinese population. A total of 412 subjects, including 206 patients with osteosarcoma and 206 healthy controls, were recruited and were assessed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) in this study. Significant differences of genotype distribution were observed between osteosarcoma cases and controls at the IL-6 −174 G/C genotypes. Compared with the homozygote GG, the heterozygous GC genotype was associated with significantly increased risk for osteosarcoma (odds ratio [OR] = 1.58, 95 % confidence interval [CI] = 1.13–3.05, p = 0.028); the CC genotype was associated with increased risk for osteosarcoma (OR = 1.57, 95 % CI = 1.21–3.26, p = 0.022). Moreover, the genotype CC of IL-6 −174 G/C carried a higher risk of osteosarcoma metastasis and later Enneking stages, compared with the GG genotype. The IL-6 −174 G/C genotype was associated with risk for development and metastasis of osteosarcoma in Chinese Han population.


IL-6 Osteosarcoma Single-nucleotide polymorphism Susceptibility 


  1. 1.
    Kramárová E, Stiller CA. The international classification of childhood cancer. Int J Cancer. 1996;68:759–65.CrossRefPubMedGoogle Scholar
  2. 2.
    Marina N, Gebhardt M, Teot L, Gorlick R. Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 2004;9:422–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Fletcher CD, Unni KK, Mertens F. Pathology and genetics of tumours of soft tissue and bone. 2002. Iarc.Google Scholar
  4. 4.
    Bai SB, Chen HX, Bao YX, Luo X, Zhong JJ. Predictive impact of common variations in DNA repair genes on clinical outcome of osteosarcoma. APJCP. 2013;14:3677–80.PubMedGoogle Scholar
  5. 5.
    Chou AJ, Gorlick R. Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev Anticancer Ther. 2006;6:1075–85.CrossRefPubMedGoogle Scholar
  6. 6.
    Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382:889–99.CrossRefPubMedGoogle Scholar
  7. 7.
    Lukaszewicz M, Mroczko B, Szmitkowski M. Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease. Pol Arch Med Wewn. 2007;117:247–51.PubMedGoogle Scholar
  8. 8.
    Crohns M et al. Cytokines in bronchoalveolar lavage fluid and serum of lung cancer patients during radiotherapy—association of interleukin-8 and VEGF with survival. Cytokine. 2010;50:30–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Culig Z et al. Interleukin-6 regulation of prostate cancer cell growth. J Cell Biochem. 2005;95:497–505.CrossRefPubMedGoogle Scholar
  10. 10.
    Giannitrapani L et al. Genetic association of interleukin-6 polymorphism (−174G/C) with chronic liver diseases and hepatocellular carcinoma. World J Gastroenterol. 2013;19:2449–55.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hefler LA et al. An interleukin-6 gene promoter polymorphism influences the biological phenotype of ovarian cancer. Cancer Res. 2003;63:3066–8.PubMedGoogle Scholar
  12. 12.
    Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B. Association of interleukin-6 (−174G > C) promoter polymorphism with risk of squamous cell esophageal cancer and tumor location: an exploratory study. Clin Immunol. 2008;128:199–204.CrossRefPubMedGoogle Scholar
  13. 13.
    Yang M, Li C, Li M. Association of interleukin-6 (−174 G/C) polymorphism with the prostate cancer risk: a meta-analysis. Biomed Rep. 2014;2:637–43.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Landi S, Moreno V, Gioia-Patricola L, Guino E, Navarro M, de Oca J, et al. Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activatedreceptor gamma with colorectal cancer. Cancer Res. 2003;63:3560–6.PubMedGoogle Scholar
  15. 15.
    Vairaktaris E, Yiannopoulos A, Vylliotis A, Yapijakis C, Derka S, Vassiliou S, et al. Strong association of interleukin-6 −174 G > C promoter polymorphism with increased risk of oral cancer. Int J Biol Markers. 2006;21:246–50.CrossRefPubMedGoogle Scholar
  16. 16.
    Shi WJ, Liu H, Wu D, Tang ZH, Shen YC, Guo L. Stratification analysis and case–control study of relationships between interleukin-6 gene polymorphisms and cervical cancer risk in a Chinese population. Asian Pac J CancerPrev. 2014;15:7357–62.CrossRefGoogle Scholar
  17. 17.
    Boerman I, Selvarajah GT, Nielen M, Kirpensteijn J. Prognostic factors in canine appendicular osteosarcoma—a meta-analysis. BMC Vet Res. 2012;8:56.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, et al. miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 2012;72:1865–77.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Teng JW, Yang ZM, Li J, Xu B. Predictive role of glutathione S-transferases (GSTs) on the prognosis of osteosarcoma patients treated with chemotherapy. Pak J Med Sci. 2013;29:1182–6.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zarogoulidis P et al. Interleukin-6 cytokine: a multifunctional glycoprotein for cancer. Immunol Res. 2013;9(62):16535.Google Scholar
  21. 21.
    Ara T, Declerck YA. Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer. 2010;46(7):1223–31.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Gomes M, Coelho A, Araújo A, Azevedo A, Teixeira AL, Catarino R, et al. IL-6 polymorphism in non-small cell lung cancer: a prognostic value? Tumour Biol. 2015;36:3679–84.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Yunlong Qi
    • 1
    Email author
  • Chengbin Zhao
    • 1
  • Hongxi Li
    • 1
  • Benning Zhang
    • 2
  • Kazuhiro Tada
    • 2
  • Hiroyuki Abe
    • 3
  • Midori Tada
    • 4
  1. 1.Department of OrthopedicsThe Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of Immunology, The Institute of Medical OncologyHarbin Medical UniversityHarbinChina
  3. 3.Kudan Clinic, The Institute of Medical OncologyKudanJapan
  4. 4.Department of ImmunologyThe Institute of Medical OncologyKudanJapan

Personalised recommendations