Skip to main content
SpringerLink
Log in

Association of OX40 gene polymorphisms (rs17568G/A and rs229811A/C) with head and neck squamous cell carcinoma

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading incident cancer worldwide. In this study, we aimed to investigate the possible association of OX40 gene polymorphisms, rs17568G/A and rs229811A/C, with susceptibility to HNSCC and its clinicopathological features. Two hundred and two HNSCC patients and 200 healthy age–sex matched individuals were enrolled. rs17568G/A and rs229811A/C polymorphisms in OX40 gene were genotyped using RFLP–PCR method. We observed more than 2 times increased risk for squamous cell carcinoma development in nose and paranasal sinuses among individuals who inherited GG genotype at rs17568 region (OR 2.29; CI 1.01–5.20; P = 0.035). Considering rs2298211 SNP, AA genotype was also observed with higher frequency, in comparison with other two genotypes (AC or CC), among patients with HNSCC originated from these regions (P = 0.003). Besides, we observed that patients with C allele at this locus (AC and CC genotypes) have tumors with significantly higher histological grade (P = 0.042). Our findings suggest the possible association of rs17568 GG genotype, as well as rs2298211 AA genotype with susceptibility to develop squamous cell carcinoma in the nose and sinonasal cavities.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. American Cancer Society (2015) Cancer facts and figures 2015. American Cancer Society, Atlanta

    Google Scholar 

  2. Bauman JE, Ferris RL (2014) Integrating novel therapeutic monoclonal antibodies into the management of head and neck cancer. Cancer 120(5):624–632. https://doi.org/10.1002/cncr.28380

    Article  CAS  PubMed  Google Scholar 

  3. Badoual C, Sandoval F, Pere H, Hans S, Gey A, Merillon N, Van Ryswick C, Quintin-Colonna F, Bruneval P, Brasnu D, Fridman WH, Tartour E (2010) Better understanding tumor-host interaction in head and neck cancer to improve the design and development of immunotherapeutic strategies. Head Neck 32(7):946–958. https://doi.org/10.1002/hed.21346

    Article  PubMed  Google Scholar 

  4. Gildener-Leapman N, Ferris RL, Bauman JE (2013) Promising systemic immunotherapies in head and neck squamous cell carcinoma. Oral Oncol 49(12):1089–1096. https://doi.org/10.1016/j.oraloncology.2013.09.009

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chen L, Flies DB (2013) Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 13(4):227–242. https://doi.org/10.1038/nri3405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Croft M, So T, Duan W, Soroosh P (2009) The significance of OX40 and OX40L to T cell biology and immune disease. Immunol Rev 229(1):173–191. https://doi.org/10.1111/j.1600-065X.2009.00766.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vu MD, Xiao X, Gao W, Degauque N, Chen M, Kroemer A, Killeen N, Ishii N, Li XC (2007) OX40 costimulation turns off Foxp3+ Tregs. Blood 110(7):2501–2510. https://doi.org/10.1182/blood-2007-01-070748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Xiao X, Gong W, Demirci G, Liu W, Spoerl S, Chu X, Bishop DK, Turka LA, Li XC (2012) New insights on OX40 in the control of T cell immunity and immune tolerance in vivo. J Immunol (Baltimore, MD 1950) 188(2):892–901. https://doi.org/10.4049/jimmunol.1101373

    Article  CAS  Google Scholar 

  9. Bell RB, Leidner RS, Crittenden MR, Curti BD, Feng Z, Montler R, Gough MJ, Fox BA, Weinberg AD, Urba WJ (2016) OX40 signaling in head and neck squamous cell carcinoma: overcoming immunosuppression in the tumor microenvironment. Oral Oncol 52:1–10. https://doi.org/10.1016/j.oraloncology.2015.11.009

    Article  CAS  PubMed  Google Scholar 

  10. Redmond WL, Linch SN, Kasiewicz MJ (2014) Combined targeting of costimulatory (OX40) and coinhibitory (CTLA-4) pathways elicits potent effector T cells capable of driving robust antitumor immunity. Cancer Immunol Res 2(2):142–153. https://doi.org/10.1158/2326-6066.CIR-13-0031-T

    Article  CAS  PubMed  Google Scholar 

  11. Aspeslagh S, Postel-Vinay S, Rusakiewicz S, Soria JC, Zitvogel L, Marabelle A (2016) Rationale for anti-OX40 cancer immunotherapy. Eur J Cancer 52:50–66. https://doi.org/10.1016/j.ejca.2015.08.021

    Article  CAS  PubMed  Google Scholar 

  12. Bulliard Y, Jolicoeur R, Zhang J, Dranoff G, Wilson NS, Brogdon JL (2014) OX40 engagement depletes intratumoral Tregs via activating FcgammaRs, leading to antitumor efficacy. Immunol Cell Biol 92(6):475–480. https://doi.org/10.1038/icb.2014.26

    Article  CAS  PubMed  Google Scholar 

  13. Rancoule C, Vallard A, Espenel S, Guy JB, Xia Y, El Meddeb Hamrouni A, Rodriguez-Lafrasse C, Chargari C, Deutsch E, Magne N (2016) Immunotherapy in head and neck cancer: harnessing profit on a system disruption. Oral Oncol. https://doi.org/10.1016/j.oraloncology.2016.09.002

    Article  PubMed  Google Scholar 

  14. Liu R, Qiao Y, Liu Y, Li X, Chen Y, Qiang O, Bai H (2013) Genetic variation in the OX40L/OX40 system and plasma lipid and lipoprotein levels in a Chinese hyper triglyceridemic population. Genetic Test Mol Biomark 17(3):207–213. https://doi.org/10.1089/gtmb.2012.0239

    Article  CAS  Google Scholar 

  15. Ria M, Eriksson P, Boquist S, Ericsson CG, Hamsten A, Lagercrantz J (2006) Human genetic evidence that OX40 is implicated in myocardial infarction. Biochem Biophys Res Commun 339(3):1001–1006. https://doi.org/10.1016/j.bbrc.2005.11.092

    Article  CAS  PubMed  Google Scholar 

  16. Mashimo Y, Suzuki Y, Hatori K, Tabara Y, Miki T, Tokunaga K, Katsuya T, Ogihara T, Yamada M, Takahashi N, Makita Y, Nakayama T, Soma M, Hirawa N, Umemura S, Ohkubo T, Imai Y, Hata A (2008) Association of TNFRSF4 gene polymorphisms with essential hypertension. J Hypertens 26(5):902–913. https://doi.org/10.1097/HJH.0b013e3282f6a65e

    Article  CAS  PubMed  Google Scholar 

  17. Chen Y, Zhang L, Huang H, Liu R, Li X, Qiang O, Zeng Z (2011) Association of OX40 and OX40L gene polymorphisms with acute coronary syndrome in a Han Chinese population. DNA Cell Biol 30(8):597–602. https://doi.org/10.1089/dna.2010.1201

    Article  CAS  PubMed  Google Scholar 

  18. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP (2017) The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 67(2):93–99. https://doi.org/10.3322/caac.21388

    Article  PubMed  Google Scholar 

  19. Excoffier L, Laval G, Schneider S (2005) Arlequin ver. 3.0: an integrated software package for population genetics data analysis. Evol Bioinform Online 1:47–50

    Article  CAS  Google Scholar 

  20. Croft M (2010) Control of immunity by the TNFR-related molecule OX40 (CD134). Annu Rev Immunol 28:57–78. https://doi.org/10.1146/annurev-immunol-030409-101243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. rs17568 https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=17568

  22. Huang Q, Yang QD, Tan XL, Feng J, Tang T, Xia J, Zhang L, Huang L, Bai YP, Liu YH (2014) Absence of association between atherosclerotic cerebral infarction and TNFSF4/TNFRSF4 single nucleotide polymorphisms rs1234313, rs1234314 and rs17568 in a Chinese population. J Int Med Res 42(2):436–443. https://doi.org/10.1177/0300060514521154

    Article  CAS  PubMed  Google Scholar 

  23. Maalhagh M, Shojaei M, Erfanian S, Sotoodeh Jahromi A, Sanie MS, Yusefi A, Zabetian H, Hakimelahi H, Madani A, Hojjat-Farsangi M (2016) Lack of association between rs17568 polymorphism in OX40 gene and myocardial infarction, Southern of Iran. Glob J Health Sci 8(6):41–46. https://doi.org/10.5539/gjhs.v8n6p41

    Article  Google Scholar 

  24. Beule AG (2010) Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses. GMS Curr Topics Otorhinolaryngol Head Neck Surg 9:Doc07. https://doi.org/10.3205/cto000071

    Article  Google Scholar 

  25. Squier CA, Kremer MJ (2001) Biology of oral mucosa and esophagus. J Natl Cancer Inst Monogr (29):7–15

  26. Levendoski EE, Leydon C, Thibeault SL (2014) Vocal fold epithelial barrier in health and injury: a research review. J Speech Lang Hear Res JSLHR 57(5):1679–1691. https://doi.org/10.1044/2014_JSLHR-S-13-0283

    Article  PubMed  Google Scholar 

  27. Bulmer DM, Ali MS, Brownlee IA, Dettmar PW, Pearson JP (2010) Laryngeal mucosa: its susceptibility to damage by acid and pepsin. Laryngoscope 120(4):777–782. https://doi.org/10.1002/lary.20665

    Article  PubMed  Google Scholar 

  28. Pezzuto F, Buonaguro L, Caponigro F, Ionna F, Starita N, Annunziata C, Buonaguro FM, Tornesello ML (2015) Update on head and neck cancer: current knowledge on epidemiology, risk factors, molecular features and novel therapies. Oncology 89(3):125–136. https://doi.org/10.1159/000381717

    Article  PubMed  Google Scholar 

  29. Bonneterre V, Deschamps E, Persoons R, Bernardet C, Liaudy S, Maitre A, de Gaudemaris R (2007) Sino-nasal cancer and exposure to leather dust. Occup Med 57(6):438–443. https://doi.org/10.1093/occmed/kqm050

    Article  Google Scholar 

  30. Luce D, Leclerc A, Begin D, Demers PA, Gerin M, Orlowski E, Kogevinas M, Belli S, Bugel I, Bolm-Audorff U, Brinton LA, Comba P, Hardell L, Hayes RB, Magnani C, Merler E, Preston-Martin S, Vaughan TL, Zheng W, Boffetta P (2002) Sinonasal cancer and occupational exposures: a pooled analysis of 12 case-control studies. Cancer Causes Control CCC 13(2):147–157

    Article  PubMed  Google Scholar 

  31. Lewis JS Jr, Westra WH, Thompson LD, Barnes L, Cardesa A, Hunt JL, Williams MD, Slootweg PJ, Triantafyllou A, Woolgar JA, Devaney KO, Rinaldo A, Ferlito A (2014) The sinonasal tract: another potential “hot spot” for carcinomas with transcriptionally-active human papillomavirus. Head Neck Pathol 8(3):241–249. https://doi.org/10.1007/s12105-013-0514-4

    Article  PubMed  Google Scholar 

  32. Gilchrist MA, Chen WC, Shah P, Landerer CL, Zaretzki R (2015) Estimating gene expression and codon-specific translational efficiencies, mutation biases, and selection coefficients from genomic data alone. Genome Biol Evol 7(6):1559–1579. https://doi.org/10.1093/gbe/evv087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Qian W, Yang JR, Pearson NM, Maclean C, Zhang J (2012) Balanced codon usage optimizes eukaryotic translational efficiency. PLoS Genet 8(3):e1002603. https://doi.org/10.1371/journal.pgen.1002603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. rs2298211 https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=2298211

Download references

Funding

The present study was financially supported by grants from Shiraz University of Medical Sciences, Shiraz, Iran [Grant No. 89-2094] and Shiraz Institute for Cancer Research (ICR-100-500).

Author information

Author notes

  1. Zahra Faghih and Shabnam Abtahi have contributed equally to this work.

Authors and Affiliations

  1. Cancer Immunology Group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Zahra Faghih

  2. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Shabnam Abtahi

  3. Department of Otolaryngology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Bijan Khademi

  4. School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Farzaneh Nikfarjam

  5. Department of Immunology and Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box 71345-1798, Shiraz, Iran

    Nasrollah Erfani

Authors
  1. Zahra Faghih
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shabnam Abtahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bijan Khademi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Farzaneh Nikfarjam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nasrollah Erfani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nasrollah Erfani.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Faghih, Z., Abtahi, S., Khademi, B. et al. Association of OX40 gene polymorphisms (rs17568G/A and rs229811A/C) with head and neck squamous cell carcinoma. Mol Biol Rep 46, 2609–2616 (2019). https://doi.org/10.1007/s11033-019-04602-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-04602-3

Keywords

Search

Navigation