Polymorphism -308 of TNFα gene and its local expression in preinvasive lesions and cervical cancer in Zulia state, Venezuela.
Polymorphism -308 of TNFα gene and its local expression in preinvasive lesions and cervical cancer in Zulia state, Venezuela.
Keywords:
cervical cancer, TNFα, -308 polymorphism of TNFα agene, cervical intraepithelial neoplasia
Abstract
Cervical cancer (CC) is a public health problem worldwide, and it represents the first cause of mortality in Venezuelan women between 25 to 44 years of age. The tumor necrosis factor alpha (TNFα) is a proinflammatory cyto-kine. Its expression is at the transcriptional level and some polymorphisms have been associated with the progression of some types of cancer, among these, the CC. The objective of the present study was to characterize the -308 poly-morphism of the TNFa gene and its local expression in preinvasive lesions and CC. Peripheral blood DNA samples and cervical biopsies from 8 healthy women and 33 with cervical lesions were analyzed, DNA was genotyped by PCR-RFLP using restriction enzymes (NcoI), and immunohistochemical labeling was used for its expression in tissues. The -308 polymorphism of the TNF-a gene was found in Hardy-Weimberg equilibrium for both, individuals and lesions, as well as for healthy individuals. It was found that the most frequent genotype was AA (60.6%), while the genotype A/G accounted for 39.4% of the total patients with lesion and no G/G genotype was detected. TNF expression is by cellular cells in heterogeneous tissues, statistically significant differences were observed be-tween the inflammatory group and CIN II (p <0.045). The results reveal an as-sociation between the A allele of the -308 polymorphism of the TNFa gene and the development of preinvasive lesions, with an OR = 1.538, with a confidence interval of 95% ranging from 0.32-7.26 with a p = 0.58.
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References
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Calhoun E, McGovern R, Janney C, Cerhan J, Iturria S, Smith D, Gostout B, Persing D. Host genetic polymorphism analysis in cer- vical cancer. Clin Chem 2000; 48(8):1218-1224.
Stanczuk G, Sibanda E, Tswana S, Bergs- trom S. Polymorphism at the -308-promoter position of the tumor necrosis factor alpha (TNF-alpha) gene and cervical cancer. Int J Gynecol Cancer 2003; 13(2):148-153.
Ghaderi M, Nikitina L, Peacock C, Hjelm- strom P, Hallmans G, Wiklund F, Lenner P, Blackwell J, Dillner J, Sanjeevi C. Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden. Epidemiol Biomarkers Prev 2001; 9(10):1067-1070.
Chagas B, Lima R, Paiva Júnior S, Silva R, Cordeiro M, Silva N, Batista M, Silva A, Gurgel A, Freitas A. Significant association between IL10-1082/-819 and TNF-308 ha- plotypes and the susceptibility to cervical carcinogenesis in women infected by human papillomavirus. Cytokine 2019;113:99-104.
Vandana G, Constant D, Hoffman M, Williamson A. The allelic distribution of -308 tumor necrosis factor-alpha gene polymorphism in South African women with cervical cancer and control women. BMC Cancer 2006; 6: 24.
Miller A, Dykes D, Polesky H. A simple sal- ting out procedure for extraction DNA from human nucleated cells. Nucl Acid Res 1988; 16(3): 1215.
Ye S, Dhillon S, Ke X, Collins A, Day I. An efficient procedure of genotyping single nucleotide polymorphism. Nucleic Acids Res 2001; 29(17):88-96.
Richard R. Influence of diagnostic and the- rapeutic procedures on the distribution of cervical intraepithelial neoplasias. Cancer 1996; 19(11): 1635-1638.
Acosta O, Solano L, Oré D, Salazar A, San- doval J, Fujita R. Polimorfismo -308 G/A en la región promotora del gen factor de necrosis tumoral alfa (TNFA) en diferentes subpoblaciones peruanas. Revista Horizonte Médico 2010, 10:1.
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Rotar I, Mureșan D, Radu P, Petrișor F, Apostol S, Tanc M, Butuza C, Stamatian F. TNF-α 308 G/A polymorphism and cer- vical intraepithelial neoplasia. Anticancer Res 2014; 34: 373-378.
Haoshan L, Jun T, Hailing C, Hongxia Z, Dongli Z. Association of tumor necrosis factor alpha polymorphisms with cervical cancer in a Chinese population. Int J Clin Exp Pathol 2016; 9(2):2200-2207.
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.
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 can- cer. Int Immunopharmacol 2019; 66:154-161.
Callejas D. Caracterización de la Respues- ta Inmunitaria Inflamatoria en el Cuello Uterino en Pacientes con Displasias de Cérvix. Tesis doctoral, Universidad de Alcalá de Henares, 2011. Disponible en: http:// dspace.uah.es/dspace/bitstream/hand- le/10017/14301/Tesis%20Doctoral%20 Diana%20Callejas.pdf?sequence=1.
Ma J, Cheng P, Chen X, Zhou C, Zheng W. Mining of prognosis-related genes in cervical squamous cell carcinoma immune mi- croenvironment. Peer J 2020; 8:e9627.
Guo L, Hua K. Cervical Cancer: emerging immune landscape and treatment. Onco Targets Ther 2020; 13:8037-8047.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: Cancer J Clin 2019; 69(1):7–34.
Capote Negrin LG. Epidemiology of cervical cancer in Latin America. Ecancermedicalscience 2015; 9:577.
Ministerio del Poder Popular para la Salud. Anuario de Mortalidad 2013. Disponible en: http://www.mpps.gob.ve/ index.php?option=com_phocadownloa d&view=categor y&id=11:anuarios-de- mortalidad&Itemid=915. Diciembre 2015.
Ministerio de Poder Popular para la Salud. Anuario de Mortalidad 2014. Disponible en: https://www.ovsalud.org/descargas/publi- caciones/documentos-oficiales/Anuario-Mortalidad-2014.pdf. 2018
Roszak A, Misztal M, Sowinska A, Jago-dzinski P. TNFα-308 G/A as risk market of cervical cancer progression in the Polish population. Mol Diagn Ther 2015; 19:53-57.
Li X, Yin G, Li J, Wu A, Yuan Z, Liang J, Sun Q. The correlation between TNF-α promoter gene polymorphism and genetic susceptibility to cervical cancer. Technol Cancer Res Treat 2018; 17:1533033818782793.
Carrero Y, Callejas D, Mindiola R, Pardo T, Atencio R, Araujo M. Respuesta inmunitaria en cuello uterino: Infección por VPH y neoplasia intraepitelial cervical. Acta Científica Estudiantil 2006; 4(3):125-136.
Szlosarek P, Charles K, Balkwill F. Tumor necrosis factor-α as a tumor promoter. Eur J Cancer 2006; 42(6):745-750.
Shishodia S, Majumdar S, Banerjee S, Aggarwal B. Ursolic acid inhibits nuclear factor-κB activation induced by carcino- genic agents through suppression of IκBα kinase and p65 phosporylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res 2003; 63(15):4375–4383.
Mota F, Rayment S, Chong A, Singer A, Chain B. The antigen-presenting environment in normal and human papillomavirus- related premalignant cervical epithelium. Clin Exp Immunol 1999; 116(1):33-40.
Tjiong M, Van der Vange N, Ten Kate F, Tjong A, Schegget J, Burger M. Increased IL -6 and IL -8 levels in cervicovaginal secre- tions of patients with cervical cancer. Gyne- col Oncol 1999; 73(2):285-291.
Yi F, Shi X, Pei X, Wu X. Tumor necrosis factor-alpha-308 gene promoter polymorphism associates with survival of cancer patients: A meta-analysis. Medicine (Balti- more) 2018;97(45):e13160.
Deshpande A, Nolan J, White P, Valdez Y, Hunt W, Peyton C, Wheeler C. TNF-a promo- ter polymorphisms and susceptibility to human papillomavirus 16-associated cervical cancer. J Infect Dis 2005; 191(6):969-976.
Tjiong M, Van der Vange N, TerSchegget J, Burger M, Ten Kate F, Out T. Cytokines in cervicovaginal washing fluid from patients with cervical neoplasia. Cytokine 2001; 14(6):357-360.
Kroeger K, Carville K, Abraham L. The-308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol 1997; 34(5):391-399.
Chen G, Wilson R, Wang S, Zheng H, Walker J, McKillop J. Tumor necrosis factor alpha (TNF-α) gene polymorphism and expression in pre-eclampsia. Clin Exp Im- munol 1996; 104(1):154-159.
Calhoun E, McGovern R, Janney C, Cerhan J, Iturria S, Smith D, Gostout B, Persing D. Host genetic polymorphism analysis in cer- vical cancer. Clin Chem 2000; 48(8):1218-1224.
Stanczuk G, Sibanda E, Tswana S, Bergs- trom S. Polymorphism at the -308-promoter position of the tumor necrosis factor alpha (TNF-alpha) gene and cervical cancer. Int J Gynecol Cancer 2003; 13(2):148-153.
Ghaderi M, Nikitina L, Peacock C, Hjelm- strom P, Hallmans G, Wiklund F, Lenner P, Blackwell J, Dillner J, Sanjeevi C. Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden. Epidemiol Biomarkers Prev 2001; 9(10):1067-1070.
Chagas B, Lima R, Paiva Júnior S, Silva R, Cordeiro M, Silva N, Batista M, Silva A, Gurgel A, Freitas A. Significant association between IL10-1082/-819 and TNF-308 ha- plotypes and the susceptibility to cervical carcinogenesis in women infected by human papillomavirus. Cytokine 2019;113:99-104.
Vandana G, Constant D, Hoffman M, Williamson A. The allelic distribution of -308 tumor necrosis factor-alpha gene polymorphism in South African women with cervical cancer and control women. BMC Cancer 2006; 6: 24.
Miller A, Dykes D, Polesky H. A simple sal- ting out procedure for extraction DNA from human nucleated cells. Nucl Acid Res 1988; 16(3): 1215.
Ye S, Dhillon S, Ke X, Collins A, Day I. An efficient procedure of genotyping single nucleotide polymorphism. Nucleic Acids Res 2001; 29(17):88-96.
Richard R. Influence of diagnostic and the- rapeutic procedures on the distribution of cervical intraepithelial neoplasias. Cancer 1996; 19(11): 1635-1638.
Acosta O, Solano L, Oré D, Salazar A, San- doval J, Fujita R. Polimorfismo -308 G/A en la región promotora del gen factor de necrosis tumoral alfa (TNFA) en diferentes subpoblaciones peruanas. Revista Horizonte Médico 2010, 10:1.
Barbisan G, Pérez L, Contreras A, Goli- jow C, TNF-α and IL -10 promoter polymor- phisms, HPV infection, and cervical cancer risk. Tumor Biol 2012; 33:1549–1556. Doi 10.1007/s13277-012-0408-1.
Rotar I, Mureșan D, Radu P, Petrișor F, Apostol S, Tanc M, Butuza C, Stamatian F. TNF-α 308 G/A polymorphism and cer- vical intraepithelial neoplasia. Anticancer Res 2014; 34: 373-378.
Haoshan L, Jun T, Hailing C, Hongxia Z, Dongli Z. Association of tumor necrosis factor alpha polymorphisms with cervical cancer in a Chinese population. Int J Clin Exp Pathol 2016; 9(2):2200-2207.
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.
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 can- cer. Int Immunopharmacol 2019; 66:154-161.
Callejas D. Caracterización de la Respues- ta Inmunitaria Inflamatoria en el Cuello Uterino en Pacientes con Displasias de Cérvix. Tesis doctoral, Universidad de Alcalá de Henares, 2011. Disponible en: http:// dspace.uah.es/dspace/bitstream/hand- le/10017/14301/Tesis%20Doctoral%20 Diana%20Callejas.pdf?sequence=1.
Published
2021-02-23
How to Cite
Castro Barrios, E. C., Pardo Govea, T., Carrero Castillo, Y., Quintero Ferrer, J. M., Sánchez Caridad, Y., Posada Bonilla, R. E., Fernández Mestre, M., & Alaña Piña, F. (2021). Polymorphism -308 of TNFα gene and its local expression in preinvasive lesions and cervical cancer in Zulia state, Venezuela.: Polymorphism -308 of TNFα gene and its local expression in preinvasive lesions and cervical cancer in Zulia state, Venezuela. Investigación Clínica, 61(4), 335-348. https://doi.org/10.22209/IC.v61n4a04
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