Tumor Biology

, Volume 36, Issue 5, pp 3979–3984 | Cite as

Association between six genetic variants of IL-17A and IL-17F and cervical cancer risk: a case–control study

  • Qiongying Lv
  • Dingjun Zhu
  • Juan Zhang
  • Yuexiong Yi
  • Shujuan Yang
  • Wei Zhang
Research Article


We conducted a case–control study to estimate association between six common single nucleotide polymorphisms (SNPs) and risk of cervical cancer and evaluate the interaction between IL-17 gene polymorphisms and environmental factors in cervical cancer patients. This study included 264 consecutive primary cervical cancer patients and 264 age-matched controls. The genotypes of IL-17A rs2275913, rs3748067, and rs3819025 and IL-17A rs763780, rs9382084, and rs1266828 were analyzed using polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP) assay. By logistic regression analysis, we found that individuals with AA genotype of rs2275913 were correlated with increased risk of cervical cancer when compared with GG genotype, and the odds ratio (OR) (95 % confidence interval (CI)) for AA genotype was 2.34 (1.24–4.49). By stratified analysis, individuals with AA genotype of rs2275913 were significantly associated with increased risk of cervical cancer in HPV-16- or HPV-18-infected patients when compared with GG genotype, and the OR (95 % CI) was 4.11 (1.14–22.33). In this case–control study, we suggest that rs2275913 may play an important role in the development of cervical cancer, especially in HPV-16- or HPV-18-infected patients.


Interleukin-17 Single nucleotide polymorphism Cervical cancer 


  1. 1.
    International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012.
  2. 2.
    Wen C. China’s plans to curb cervical cancer. Lancet Oncol. 2005;6:139–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Schlecht NF, Kulaga S, Robitaille J, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA. 2001;286:3106–14.CrossRefPubMedGoogle Scholar
  4. 4.
    Woodman CB, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet. 2001;357:1831–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Quan Y, Zhou B, Wang Y, et al. Association between IL17 polymorphisms and risk of cervical cancer in Chinese women. Clin Dev Immunol. 2012;2012:258293.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Shi TY, Zhu ML, He J, et al. Polymorphisms of the Interleukin 6 gene contribute to cervical cancer susceptibility in Eastern Chinese women. Hum Genet. 2013;132(3):301–12.CrossRefPubMedGoogle Scholar
  7. 7.
    de Waal MR, Haanen J, Spits H, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991;174(4):915–24.CrossRefGoogle Scholar
  8. 8.
    Fernandes AP, Gonçalves MA, Duarte G, Cunha FQ, Simões RT, Donadi EA. HPV16, HPV18, and HIV infection may influence cervical cytokine intralesional levels. Virology. 2005;334(2):294–8.CrossRefPubMedGoogle Scholar
  9. 9.
    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 Cancer Prev. 2014;15(17):7357–62.CrossRefPubMedGoogle Scholar
  10. 10.
    Chen X, Han S, Wang S, et al. Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clin Cancer Res. 2009;15(1):400–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Yang YC, Chang TY, Chen TC, Chang SC, Lin WS, Lee YJ. Genetic variants in interleukin-18 gene and risk for cervical squamous cell carcinoma. Hum Immunol. 2013;74(7):882–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Chagas BS, Gurgel AP, da Cruz HL, et al. An interleukin-10 gene polymorphism associated with the development of cervical lesions in women infected with human papillomavirus and using oral contraceptives. Infect Genet Evol. 2013;19:32–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21(4):467–76.CrossRefPubMedGoogle Scholar
  14. 14.
    Kawaguchi M, Adachi M, Oda N, Kokubu F, Huang SK. IL-17 cytokine family. J Allergy Clin Immunol. 2004;114(6):1265–73. quiz 1274.CrossRefPubMedGoogle Scholar
  15. 15.
    Wu D, Wu P, Huang Q, Liu Y, Ye J, Huang J. Interleukin-17: a promoter in colorectal cancer progression. Clin Dev Immunol. 2013;2013:436307.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Cua DJ, Tato CM. Innate il-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479–89.CrossRefPubMedGoogle Scholar
  17. 17.
    Yang L, Qi Y, Hu J, Tang L, Zhao S, Shan B. Expression of Th17 cells in breast cancer tissue and its association with clinical parameters. Cell Biochem Biophys. 2012;62:153–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Lan C, Huang X, Lin S, et al. High density of IL-17-producing cells is associated with improved prognosis for advanced epithelial ovarian cancer. Cell Tissue Res. 2013;352:351–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Meng XY, Zhou CH, Ma J, Jiang C, Ji P. Expression of interleukin-17 and its clinical significance in gastric cancer patients. Med Oncol. 2012;29:3024–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Chechlinska M, Kowalewska M, Nowak R. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nat Rev Cancer. 2010;10:2–3.CrossRefPubMedGoogle Scholar
  21. 21.
    Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional specialization of interleukin-17 family members. Immunity. 2011;34:149–62.CrossRefPubMedGoogle Scholar
  22. 22.
    Matsuzaki G, Umemura M. Interleukin-17 as an effector molecule of innate and acquired immunity against infections. Microbiol Immunol. 2007;51:1139–47.CrossRefPubMedGoogle Scholar
  23. 23.
    Kao CY, Chen Y, Thai P, et al. Il-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol. 2004;173:3482–91.CrossRefPubMedGoogle Scholar
  24. 24.
    Kaabachi W, ben Amor A, Kaabachi S, Rafrafi A, Tizaoui K, Hamzaoui K. Interleukin-17A and -17F genes polymorphisms in lung cancer. Cytokine. 2014;66(1):23–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Zhang X, Zheng L, Sun Y, Zhang X. Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population. Tumour Biol. 2014;35(2):1575–80.CrossRefPubMedGoogle Scholar
  26. 26.
    Omrane I, Marrakchi R, Baroudi O, et al. Significant association between interleukin-17A polymorphism and colorectal cancer. Tumour Biol. 2014;35(7):6627–32.CrossRefPubMedGoogle Scholar
  27. 27.
    Li N, Zhu Q, Li Z, et al. IL17A gene polymorphisms, serum IL-17A and IgE levels, and hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection. Mol Carcinog. 2014;53(6):447–57.CrossRefPubMedGoogle Scholar
  28. 28.
    Wang L, Jiang Y, Zhang Y, et al. Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer. PLoS One. 2012;7(3):e34400.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Chen Z, Ding J, Pang N, et al. The Th17/Treg balance and the expression of related cytokines in Uygur cervical cancer patients. Diagn Pathol. 2013;8:61.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Souza JM, Matias BF, Rodrigues CM, Murta EF, Michelin MA. IL-17 and IL-22 serum cytokine levels in patients with squamous intraepithelial lesion and invasive cervical carcinoma. Eur J Gynaecol Oncol. 2013;34(5):466–8.PubMedGoogle Scholar
  31. 31.
    Wu TC, Kurman RJ. Analysis of cytokine profiles in patients with human papillomavirus-associated neoplasms. J Natl Cancer Inst. 1997;89:185–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Kadish AS, Timmins P, Wang Y, et al. Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide. Cancer Epidemiol Biomarkers Prev. 2002;11:483–8.PubMedGoogle Scholar
  33. 33.
    Scott M, Stites DP, Moscicki AB. Th1 cytokine patterns in cervical human papillomavirus infection. Clin Diagn Lab Immunol. 1999;6:751–5.PubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Qiongying Lv
    • 1
  • Dingjun Zhu
    • 1
  • Juan Zhang
    • 1
  • Yuexiong Yi
    • 1
  • Shujuan Yang
    • 2
  • Wei Zhang
    • 1
  1. 1.First Department of GynaecologyRenmin Hospital of Wuhan UniversityWuhanChina
  2. 2.Department of Health and Social Behavior, West China School of Public HealthSichuan UniversityChengduChina

Personalised recommendations