AccScience Publishing / EJMO / Volume 6 / Issue 3 / DOI: 10.14744/ejmo.2022.78475
RESEARCH ARTICLE

The Involvement of Interleukin-10 Promoter Genetic Polymorphism in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma from North Africa

Khalid Moumad1* Wafa Khaali1,2* Abdellatif Benider3 Wided Ben Ayoub4 Mokhtar Hamdi-Cherif5 Kada Boualga6 Elham Hassen7 Amina Gihbid1 El Khalil Ben Driss2 Nadia Benchakroun3 Marilys Corbex8 Meriem Khyatti1
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1 Oncovirology Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco
2 Department of Biology, Faculty of Sciences, Abdelmalek Essaadi University, 93030 Tetouan, Morocco
3 Centre Mohamed VI de la Lutte contre le Cancer, 20360 Casablanca, Morocco
4 Association Tunisienne de Lutte Contre le Cancer, 10006 Tunis, Tunisia
5 Service d'épidémiologie, CHU de Sétif, 1900 Sétif, Algeria
6 Service de Radiothérapie Oncologique, Centre Anti-Cancer de Blida, 09000 Blida, Algeria
7 Molecular Immuno-Oncology Laboratory, Faculty of Medicine, Monastir University, 5019 Monastir, Tunisia
8 Who Regional Office for Europe, Marmorvej 51, DK-2100 Copenhagen, Denmark
EJMO 2022, 6(3), 232–240; https://doi.org/10.14744/ejmo.2022.78475
Submitted: 17 April 2022 | Accepted: 31 August 2022 | Published: 16 October 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Objectives: Interleukin-10 (IL10) is a pro-inflammatory cytokine that plays a pivotal role in inflammatory diseases as well as in the pathogenesis of diverse tumors, including nasopharyngeal carcinoma (NPC). The present study was designed to evaluate the importance of the functional promoter polymorphisms of IL10 (-1082 A>G and -592 A>C) in the development of NPC.

Methods: A total of 384 patients with NPC were recruited into this study, together with 375 matched control subjects. Polymorphisms within the promoter region of IL10 gene were analysed using PCR-RFLP method.

Results: We report a lack of association between IL10 polymorphisms and NPC in the overall population (P>0.05). However, the 1082 A>G polymorphism was significantly associated with the susceptibility to NPC among young patients (age ≤30 years). The GG genotype was found to be associated with a significantly higher risk of NPC as compared with the AA genotype among young patients (OR=2.534; 95% CI, 1.189–5.398, P=0.016).

Conclusion: The results of the present study indicate an association between IL10 -1082 GG genotype and NPC among young North African subjects. This difference in IL10 polymorphism association with different ages at the onset of NPC suggests that the younger and older onset patients are genetically different and may involve different mechanisms.

Keywords
Nasopharyngeal Carcinoma
IL10
North African population
Conflict of interest
The authors declare no potential conflict of interests.
References

1. Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 2006;15:1765–77. [CrossRef]
2. Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol 2002;12:421–9. [CrossRef]
3. Haugen M, Bray F, Grotmol T, Tretli S, Aalen OO, Moger TA. Frailty modeling of bimodal age-incidence curves of nasopharyngeal carcinoma in low-risk populations. Biostatistics 2009;10:501–14. [CrossRef]
4. Ayadi W, Khabir A, Hadhri-Guiga B, Fki L, Toumi N, Siala W, et al. North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance. Bull Cancer (Paris) 2010;97:475–82. [CrossRef]
5. Chow MT, Möller A, Smyth MJ. Inflammation and immune surveillance in cancer. Semin Cancer Biol 2012;22:23–32. [CrossRef]
6. Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y. Cytokines in cancer immunity and immunotherapy. Immunol Rev 2004;202:275–93. [CrossRef]
7. de Vries JE. Immunosuppressive and anti-inflammatory properties of interleukin 10. Ann Med 1995;27:537–41. [CrossRef] 
8. Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 2005;78:1043–51. [CrossRef]
9. Mocellin S, Panelli MC, Wang E, Nagorsen D, Marincola FM. The dual role of IL10. Trends Immunol 2003;24:36–43. [CrossRef]
10. Howell MW. Interleukin-10 Gene Polymorphisms and Cancer. Landes Bioscience; 2013. Available at: https://www.ncbi.nlm.nih.gov/books/NBK6117/. Accessed Sep 26, 2022. [CrossRef]
11. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 1989;170:2081–95. 
12. Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 1990;248:1230–4. [CrossRef]
13. Giordani L, Bruzzi P, Lasalandra C, Quaranta M, Schittulli F, Ragione FD, et al. Association of breast cancer and polymorphisms of interleukin-10 and tumor necrosis factor-α Genes. Clin Chem 2003;49:1664–7. [CrossRef]
14. Kingo K, Rätsep R, Kõks S, Karelson M, Silm H, Vasar E. Influence of genetic polymorphisms on interleukin-10 mRNA expression and psoriasis susceptibility. J Dermatol Sci 2005;37:111– 3. [CrossRef]
15. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenetics Off J Br Soc Histocompat Immunogenetics 1997;24:1–8. [CrossRef]
16. D’Alfonso S, Rampi M, Rolando V, Giordano M, Momigliano-Richiardi P. New polymorphisms in the IL10 promoter region. Genes Immun 2000;1:231–3. [CrossRef]
17. Mörmann M, Rieth H, Hua TD, Assohou C, Roupelieva M, Hu SL, et al. Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. Genes Immun 2004;5:246–55. [CrossRef]
18. Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendorp RGJ, Huizinga TWJ. Interleukin 10 secretion in relation to human IL10 locus haplotypes. Proc Natl Acad Sci 1998;95:9465–70.
19. Gibson AW, Edberg JC, Wu J, Westendorp RG, Huizinga TW, Kimberly RP. Novel single nucleotide polymorphisms in the distal IL10 promoter affect IL10 production and enhance the risk of systemic lupus erythematosus. J Immunol Baltim Md 1950 2001;166:3915–22. [CrossRef]
20. Aziz F, Chakraborty A, Liu K, Zhang T, Li X, Du R, et al. Gastric tumorigenesis induced by combining Helicobacter pylori infection and chronic alcohol through IL10 inhibition. Carcinogenesis 2022;43:126–39. [CrossRef]
21. Howell WM, Turner SJ, Bateman AC, Theaker JM. IL10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma. Genes Immun 2001;2:25–31.
22. McCarron SL, Edwards S, Evans PR, Gibbs R, Dearnaley DP, Dowe A, et al. Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res 2002;62:3369–72.
23. Roh JW, Kim MH, Seo SS, Kim SH, Kim JW, Park NH, et al. Interleukin-10 promoter polymorphisms and cervical cancer risk in Korean women. Cancer Lett 2002;184:57–63. [CrossRef]
24. Niiro H, Otsuka T, Abe M, Satoh H, Ogo T, Nakano T, et al. Epstein-Barr virus BCRF1 gene product (viral interleukin 10) inhibits superoxide anion production by human monocytes. Lymphokine Cytokine Res 1992;11:209–14.
25. Burdin N, Péronne C, Banchereau J, Rousset F. Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10. J Exp Med 1993;177:295–304. [CrossRef]
26. Vieira P, de Waal-Malefyt R, Dang MN, Johnson KE, Kastelein R, Fiorentino DF, et al. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci U S A 1991;88:1172–6. [CrossRef]
27. Stewart JP, Rooney CM. The interleukin-10 homolog encoded by Epstein-Barr virus enhances the reactivation of virus-specific cytotoxic T cell and HLA-unrestricted killer cell responses. Virology 1992;191:773–82. [CrossRef]
28. Hernández-Bello J, Oregón-Romero E, Vázquez-Villamar M, García-Arellano S, Valle Y, Padilla-Gutiérrez JR, et al. Aberrant expression of interleukin-10 in rheumatoid arthritis: Relationship with IL10 haplotypes and autoantibodies. Cytokine 2017;95:88–96. [CrossRef]
29. Hofmann SR, Laass MW, Fehrs A, Schuppan D, Zevallos VF, Salminger D, et al. IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease. Clin Immunol Orlando Fla 2018;190:15–21.
30. Hsia T-C, Chang W-S, Liang S-J, Chen W-C, Tu C-Y, Chen H-J, et al. Interleukin-10 (IL10) promoter genotypes are associated with lung cancer risk in Taiwan males and smokers. Anticancer Res 2014;34:7039–44.
31. Pooja S, Chaudhary P, Nayak LV, Rajender S, Saini KS, Deol D, et al. Polymorphic variations in IL-1β, IL-6 and IL10 genes, their circulating serum levels and breast cancer risk in Indian women. Cytokine 2012;60:122–8. [CrossRef] 
32. Singhal P, Kumar A, Bharadwaj S, Hussain S, Bharadwaj M. Association of IL10 GTC haplotype with serum level and HPV infection in the development of cervical carcinoma. Tumour Biol 2015;36:2287–98. [CrossRef]
33. Ma L, Li S, Lu Y, Zhang X, Zhao J, Qin X. A pooled analysis of the IL10-1082 A/G polymorphism and the nasopharyngeal carcinoma susceptibility. Eur Arch Otorhinolaryngol 2016;273:819–25. [CrossRef]
34. Tsai C-W, Tsai M-H, Shih L-C, Chang W-S, Lin C-C, Bau D-T. Association of interleukin-10 (IL10) promoter genotypes with nasopharyngeal carcinoma risk in Taiwan. Anticancer Res 2013;33:3391–6.
35. Wei Y-S, Kuang X-H, Zhu Y-H, Liang W-B, Yang Z-H, Tai S-H, et al. Interleukin-10 gene promoter polymorphisms and the risk of nasopharyngeal carcinoma. Tissue Antigens 2007;70:12–7.
36. Feng B-J, Jalbout M, Ayoub WB, Khyatti M, Dahmoul S, Ayad M, et al. Dietary risk factors for nasopharyngeal carcinoma in Maghrebian countries. Int J Cancer 2007;121:1550–5. [CrossRef]
37. Feng B-J, Khyatti M, Ben-Ayoub W, Dahmoul S, Ayad M, Maachi F, et al. Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa. Br J Cancer 2009;101:1207–12. [CrossRef]
38. Shih C-M, Lee Y-L, Chiou H-L, Hsu W-F, Chen W-E, Chou M-C, et al. The involvement of genetic polymorphism of IL10 promoter in non-small cell lung cancer. Lung Cancer Amst Neth 2005;50:291–7. [CrossRef]
39. Ng WT, Chan SH, Lee AWM, Lau KY, Yau TK, Hung WM, et al. Parapharyngeal extension of nasopharyngeal carcinoma: still a significant factor in era of modern radiotherapy? Int J Radiat Oncol Biol Phys 2008;72:1082–9. [CrossRef] 
40. Xiao G, Cao Y, Qiu X, Wang W, Wang Y. Influence of gender and age on the survival of patients with nasopharyngeal carcinoma. BMC Cancer 2013;13:226. [CrossRef]
41. Budiani DR, Hutahaean S, Haryana SM, Soesatyo MH, Sosroseno W. Interleukin-10 levels in Epstein-Barr virus-associated nasopharyngeal carcinoma. J Microbiol Immunol Infect 2002;35:265–8.
42. Salazar-Onfray F. Interleukin-10: a cytokine used by tumors to escape immunosurveillance. Med Oncol 1999;16:86–94. 
43. Muti G, Klersy C, Baldanti F, Granata S, Oreste P, Pezzetti L, et al. Epstein–Barr virus (EBV) load and interleukin-10 in EBV-positive and EBV-negative post-transplant lymphoproliferative disorders. Br J Haematol 2003;122:927–33. [CrossRef]
44. Eskdale J, Kube D, Tesch H, Gallagher G. Mapping of the human IL10 gene and further characterization of the 5’ flanking sequence. Immunogenetics 1997;46:120–8. [CrossRef]
45. Koss K, Satsangi J, Fanning GC, Welsh KI, Jewell DP. Cytokine (TNF alpha, LT alpha and IL10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. Genes Immun 2000;1:185– 90. [CrossRef]
46. Yasui Y, Hamajima N, Nakamura T, El-Din NS, Tajima K, Potter JD. Association of Epstein-Barr virus antibody titers with a human IL10 promoter polymorphism in Japanese women. J Autoimmune Dis 2008;5:2. [CrossRef]
47. Farhat K, Hassen E, Gabbouj S, Bouaouina N, Chouchane L. Interleukin‐10 and interferon‐gamma gene polymorphisms in patients with nasopharyngeal carcinoma. Int J Immunogenet 2008;35:197–205. [CrossRef]
48. Sousa H, Mesquita L, Ribeiro J, Catarino R, Breda E, Medeiros R. Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal. Immunobiology 2016;221:145–52. [CrossRef] 
49. Pratesi C, Bortolin MT, Bidoli E, Tedeschi R, Vaccher E, Dolcetti R, et al. Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type. Cancer Immunol Immunother CII 2006;55:23–30. [CrossRef]
50. de-Vathaire F, Sancho-Garnier H, de-Thé H, Pieddeloup C, Schwaab G, Ho JH, et al. Prognostic value of EBV markers in the clinical management of nasopharyngeal carcinoma (NPC): a multicenter follow-up study. Int J Cancer 1988;42:176–81.
51. Ben Nasr H, Chahed K, Remadi S, Zakhama A, Chouchane L. Expression and clinical significance of latent membrane protein-1, matrix metalloproteinase-1 and Ets-1 transcription factor in Tunisian nasopharyngeal carcinoma patients. Arch Med Res 2009;40:196–203. [CrossRef]
52. Klein SC, Kube D, Abts H, Diehl V, Tesch H. Promotion of IL8, IL10, TNF alpha and TNF beta production by EBV infection. Leuk Res 1996;20:633–6. [CrossRef]

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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing