Molecular Evaluation of TNF-α-308 and TNF-α-238 Polymorphisms and their Association with HPV Genotypes in Cervical Lesions
Abstract
Abstract Background: Cervical cancer is a multi-stage disease that is contaminated by a DNA virus and is involved in one or more stages in the pathogenesis process. In addition to human papillomaviruses (HPV), the tumor necrosis factor-α gene (TNF-α) is considered a major intermediate mediator of the acute inflammatory response to viruses and a gram-negative bacterium. The pro-region polymorphisms of the TNF-α gene such as -308 and -238 polymorphisms affect the expression of this gene. Therefore, this study aimed to investigate the polymorphisms of the TNF-α gene and its relationship with various genotypes of HPV in cervical lesions. Methods: In this study, 58 female patients with cervical cancer symptoms were selected, then following histopathologic studies, DNA was extracted from all specimens, and the PCR method was used to determine the types of HPV genotypes and TNF-α gene polymorphisms. Also, an ARMS-PCR reaction was performed to amplify TNF-α -308 and TNF-α -238 polymorphisms. Statistical analysis of the data was carried out by the Epi Info software version 7. 2 and Chi-Square (x2) test using SPSS ver.7.3.1.10. These lesions were categorized into metaplasia groups (93.37%), cervical intraepithelial neoplasia (CIN) I and II (20.68%), CIN III (15.51%) and squamous cell carcinoma (SCC) (25.86%). Results: In this study 58 lesions were collected and 26 of which were HPV positive. They were categorized as the following: 1 sample (4.53%) metaplasia, 7 samples (33.58%) CIN I and CIN II, 6 samples (66.66%) CIN III and 12 samples (80%) SCC. According to the results of statistical analysis, there was a significant difference between different types of HPV genotypes in different wastes. On the other hand, in contrast to the -238 polymorphism of the TNF-α gene, a significant difference was observed between the various types of -308 polymorphism of the TNF-α gene in the three groups of metaplasia, CIN, and SCC. In general, we can conclude that GG genotype testing of the -308 polymorphism of TNF-α gene and HPV types in combination with para-clinical parameters can be effective as risk factors and molecular markers for prognosis and early treatment of cervical cancer.
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14. Balkwill F. Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev. 2002;13(2):135-41
15. Niu YL, Guo Z, Zhou RH. Up-regulation of TNF-alpha in neurons of dorsal root ganglia and spinal cord during coronary artery occlusion in rats. Cytokine. 2009;47(1):23-9.
16. Calhoun ES, McGovern RM, Janney CA, Cerhan JR, Iturria SJ, Smith DI, et al. Host genetic polymorphism analysis in cervical cancer. Clin Chem. 2002;48(8):1218-24.
17. Cohn ZJ, Kim A, Huang L, Brand J and Wang H. Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells. BMC Neurosci. 2010; 10;11:72.
18. Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech. 2000;50(3):184-95.
19. Li L, Liu J, Liu C, Lu X. The correlation between TNF-α-308 gene polymorphism and susceptibility to cervical cancer. Oncol Lett. 2018;15(5):7163-7167.
20. Hajeer AH, Hutchinson IV, TNF-α gene polymorphism: Clinical and biological implications. MICROSCOPY RESEARCH AND TECHNIQUE. 2000;50: 183-258.
21. Ding C, Ji X, Chen X, Xu Y, Zhong L. TNF-α gene promoter polymorphisms contribute to periodontitis susceptibility: evidence from 46 studies. J Clin Periodontol. 2014;41(8):748-59.
22. Cao XL, Chai J, Yu YY, Tian X, Zhao JY, Yu LY, Sun ZG. Association of TNF-α gene T-1031C polymorphism with endometriosis: A meta-analysis. Am J Reprod Immunol. 2020;84(6):e13305.
23. Wang P, Wang J, Yu M, Li Z. Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis. Dis Markers. 2016;2016:4580323.
24. Thriveni K, Raju A, Ramaswamy G, Krishnamurthy S. Impact of gene polymorphism of TNF-α rs 1800629 and TNF-β rs 909253 on plasma levels of South Indian breast cancer patients. Indian J Cancer. 2018;55(2):179-183.
25. Hughes C. Cervical cancer: prevention, diagnosis, treatment and nursing care. Nurs Stand. 2009 Mar 11-17;23(27):48-56; quiz 58. doi: 10.7748/ns2009.03.23.27.48.c6838. PMID: 19338172.
26. Marzbanrad Z, Karimi-Zarchi M, Noei-Teymoordash S, Motamedinasab M, Azizi S, Noori-Ardebili S, Barahman M, Yeganegi M, Masoudi A, Alijanpour K, Aghasipour M, Aghili K, Neamatzadeh H. A Comprehensive Integration of Data Regarding the Correlation of TNF-α rs1800629 Polymorphism with Susceptibility to Cervical Cancer. Asian Pac J Cancer Prev. 2024 Apr 1;25(4):1155-1167. doi: 10.31557/APJCP.2024.25.4.1155. PMID: 38679974; PMCID: PMC11162705.
27. Niakan M, Garshasbi A, Jalali MR, Gilani M, Faghih zadeh S. Detection of human papilloma virus (HPV) in cervical cancer lesions by molecular hybridization method. Journal of Reproduction and Infertility. 2000;1(3):18-22.
28. Allameh T, Moghim S and Asadi-Zeidabadi M. A survey on the prevalence of high-risk subtypes of human papilloma virus among women with cervical neoplasia in Isfahan University of Medical Science. Arch Gynecol Obstet. 2011;284(6):1509-13.
29. Traore IMA, Zohoncon TM, Djigma FW, Compaore TR, Traore Y, Simpore J. Association of TNF-α-308G/A and IL-18 Polymorphisms with risk of HPV infection among sexually active women in Burkina Faso. Biomol Concepts. 2020;11(1):97-101.
30. Muñoz N, Bosch FX, de Sanjosé S, Tafur L, Izarzugaza I, Gili M, et al. The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain. Int J Cancer. 1992;52(5):743-9.
31. Kohaar I, Thakur N, Salhan S, Batra S, Singh V, Sharma A, et al.TNFalpha-308G/A polymorphism as a risk factor for HPV associated cervical cancer in Indian population. Cell Oncol. 2007;29(3):249-56.
32. Kroeger K, Carville K, Abraham L.The -308 tumor necrosis factor-alpha promoter Polymorphism effects transcription. Mol Immunol. 1997; 34(5): 391-399.
33. Duvlis S, Dabeski D, Cvetkovski A, Mladenovska K, Plaseska-Karanfilska D. Association of TNF-a (rs361525 and rs1800629) with susceptibility to cervical intraepithelial lesion and cervical carcinoma in women from Republic of North Macedonia. Int J Immunogenet. 2020;47(6):522-528.
34. Du GH, Wang JK, Richards JR, Wang JJ. Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer. Int Immunopharmacol. 2019;66:154-161.
35. Chagas BS, Lima RCP, Paiva Júnior SSL, Silva RCO, Cordeiro MN, Silva Neto JDC, Batista MVA, Silva AJD, Gurgel APAD, Freitas AC. Significant association between IL10-1082/-819 and TNF-308 haplotypes and the susceptibility to cervical carcinogenesis in women infected by Human papillomavirus. Cytokine. 2019;113:99-104.
2. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37 Suppl 8:S4-66.
3. Assessment of Cervical Cancer Screening and its Barriers in 18 -50 Year Old Women Referring to Asad Abad Comprehensive Health Centers Mahnaz Sharifi (MSc) 1 , Ziba Mohammadi (MSc) 2 , Zeinab Makvandi (MSc)3, * , Parisa Rostami (BSc) 4 , Ali Moradi (PhD) 5
4. Dominik S, cervical cancer. 2024. World Health Organization. Available at: URL:https://www.who.int/. Accessed Aug 20, 2024.
5. Williamson AL. Recent Developments in Human Papillomavirus (HPV) Vaccinology. Viruses. 2023 26;15(7):1440.
6. Eslami G, Rakhshan M, Fallah F, Goodarzi H. Frequency of human papillomavirus in women with cervical cancer by PCR method. Pejouhandeh 2008;13(3):231-237.
7. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8(2):e180-e190.
8. Mobini Kesheh M, Kafashi A, Bagheri G, Shahkarami MK, Mohamadi M, Nadji SA. Identification of Human Papillomavirus Type 16 among Thinprep Samples from 11 Provinces of Iran. Obstetrics, Gynecology and Infertility. 2013;16(72):22-28.
9. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010;202(12):1789-99.
10. INFORMATION CENTRE. Human Papillomavirus and Related Cancers, Fact Sheet; 2023. Available at: https://hpvcentre.net/. Accessed Aug 20, 2024.
11. Wright TC Jr, Schiffman M. Adding a test for human papillomavirus DNA to cervical-cancer screening. N Engl J Med. 2003; 6;348(6):489-90
12. Tavakoli A, Seyyed-Khorrami S, Ashrafi hafez A, Khalil nejhad A, Shohani B. Carcinogenesis: Role of Viruses in Pathogenesis of Cancers. Journal of Ilam University of Medical Sciences. 2014; 21(7): 252-265
13. Vesco KK, Whitlock EP, Eder M, Burda BU, Senger CA, Lutz K. Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155(10):698-705, W216
14. Balkwill F. Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev. 2002;13(2):135-41
15. Niu YL, Guo Z, Zhou RH. Up-regulation of TNF-alpha in neurons of dorsal root ganglia and spinal cord during coronary artery occlusion in rats. Cytokine. 2009;47(1):23-9.
16. Calhoun ES, McGovern RM, Janney CA, Cerhan JR, Iturria SJ, Smith DI, et al. Host genetic polymorphism analysis in cervical cancer. Clin Chem. 2002;48(8):1218-24.
17. Cohn ZJ, Kim A, Huang L, Brand J and Wang H. Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells. BMC Neurosci. 2010; 10;11:72.
18. Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech. 2000;50(3):184-95.
19. Li L, Liu J, Liu C, Lu X. The correlation between TNF-α-308 gene polymorphism and susceptibility to cervical cancer. Oncol Lett. 2018;15(5):7163-7167.
20. Hajeer AH, Hutchinson IV, TNF-α gene polymorphism: Clinical and biological implications. MICROSCOPY RESEARCH AND TECHNIQUE. 2000;50: 183-258.
21. Ding C, Ji X, Chen X, Xu Y, Zhong L. TNF-α gene promoter polymorphisms contribute to periodontitis susceptibility: evidence from 46 studies. J Clin Periodontol. 2014;41(8):748-59.
22. Cao XL, Chai J, Yu YY, Tian X, Zhao JY, Yu LY, Sun ZG. Association of TNF-α gene T-1031C polymorphism with endometriosis: A meta-analysis. Am J Reprod Immunol. 2020;84(6):e13305.
23. Wang P, Wang J, Yu M, Li Z. Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis. Dis Markers. 2016;2016:4580323.
24. Thriveni K, Raju A, Ramaswamy G, Krishnamurthy S. Impact of gene polymorphism of TNF-α rs 1800629 and TNF-β rs 909253 on plasma levels of South Indian breast cancer patients. Indian J Cancer. 2018;55(2):179-183.
25. Hughes C. Cervical cancer: prevention, diagnosis, treatment and nursing care. Nurs Stand. 2009 Mar 11-17;23(27):48-56; quiz 58. doi: 10.7748/ns2009.03.23.27.48.c6838. PMID: 19338172.
26. Marzbanrad Z, Karimi-Zarchi M, Noei-Teymoordash S, Motamedinasab M, Azizi S, Noori-Ardebili S, Barahman M, Yeganegi M, Masoudi A, Alijanpour K, Aghasipour M, Aghili K, Neamatzadeh H. A Comprehensive Integration of Data Regarding the Correlation of TNF-α rs1800629 Polymorphism with Susceptibility to Cervical Cancer. Asian Pac J Cancer Prev. 2024 Apr 1;25(4):1155-1167. doi: 10.31557/APJCP.2024.25.4.1155. PMID: 38679974; PMCID: PMC11162705.
27. Niakan M, Garshasbi A, Jalali MR, Gilani M, Faghih zadeh S. Detection of human papilloma virus (HPV) in cervical cancer lesions by molecular hybridization method. Journal of Reproduction and Infertility. 2000;1(3):18-22.
28. Allameh T, Moghim S and Asadi-Zeidabadi M. A survey on the prevalence of high-risk subtypes of human papilloma virus among women with cervical neoplasia in Isfahan University of Medical Science. Arch Gynecol Obstet. 2011;284(6):1509-13.
29. Traore IMA, Zohoncon TM, Djigma FW, Compaore TR, Traore Y, Simpore J. Association of TNF-α-308G/A and IL-18 Polymorphisms with risk of HPV infection among sexually active women in Burkina Faso. Biomol Concepts. 2020;11(1):97-101.
30. Muñoz N, Bosch FX, de Sanjosé S, Tafur L, Izarzugaza I, Gili M, et al. The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain. Int J Cancer. 1992;52(5):743-9.
31. Kohaar I, Thakur N, Salhan S, Batra S, Singh V, Sharma A, et al.TNFalpha-308G/A polymorphism as a risk factor for HPV associated cervical cancer in Indian population. Cell Oncol. 2007;29(3):249-56.
32. Kroeger K, Carville K, Abraham L.The -308 tumor necrosis factor-alpha promoter Polymorphism effects transcription. Mol Immunol. 1997; 34(5): 391-399.
33. Duvlis S, Dabeski D, Cvetkovski A, Mladenovska K, Plaseska-Karanfilska D. Association of TNF-a (rs361525 and rs1800629) with susceptibility to cervical intraepithelial lesion and cervical carcinoma in women from Republic of North Macedonia. Int J Immunogenet. 2020;47(6):522-528.
34. Du GH, Wang JK, Richards JR, Wang JJ. Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer. Int Immunopharmacol. 2019;66:154-161.
35. Chagas BS, Lima RCP, Paiva Júnior SSL, Silva RCO, Cordeiro MN, Silva Neto JDC, Batista MVA, Silva AJD, Gurgel APAD, Freitas AC. Significant association between IL10-1082/-819 and TNF-308 haplotypes and the susceptibility to cervical carcinogenesis in women infected by Human papillomavirus. Cytokine. 2019;113:99-104.
| Files | ||
| Issue | Vol 16 No 2 (2024) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v16i2.19428 | |
| Keywords | ||
| Keywords: Cervical neoplasm, Human Papilloma Virus, Polymorphism, Tumor Necrosis Factor-alpha | ||
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How to Cite
1.
Gharoonpour A, Rassi H, Hemati B. Molecular Evaluation of TNF-α-308 and TNF-α-238 Polymorphisms and their Association with HPV Genotypes in Cervical Lesions. Basic Clin Cancer Res. 2025;16(2):86-97.
