Abstract
Tumour necrosis factor alpha (TNF-α) is a strong pro-inflammatory cytokine with important functions on immune response to viral infections. A single nucleotide polymorphism on the −308 position of the promoter region of TNFA gene characterised by a G > A transition has been associated with different TNF-α levels and therefore with differential susceptibility for the development several diseases. A cross-sectional case–control study was performed with 509 women with cancer from the northern region of Portugal, including 205 healthy women and 337 women with different cervical lesions including invasive cervical. The −308G > A polymorphism genotyping was performed with TaqMan® SNP Genotyping Assay and studied for its association with cervical cancer development. This study showed increased frequency of the −308A allele in women with any cervical lesions. Statistical analysis revealed that −308A carriers are associated with an almost 2-fold increased risk for invasive cervical cancer development (p = 0.005; odds ratio (OR) = 1.87). Similar results were found when comparing the risk of progression between preinvasive lesions and invasive cervical cancer development (p = 0.002; OR = 2.41). Our results reveal that −308 TNFA AA individuals are at increased risk of invasive cervical cancer development and more important, that the risk is significantly increased for the progression from premalignant lesion to invasive cancer. Considering previous data and this study, this polymorphism confirms to be a significant marker in our population.
Similar content being viewed by others
References
Farrell PJ. Tumour viruses—could they be an Achilles’ heel of cancer? Eur J Cancer. 2002;38:1815–6.
Zur Hausen H. The search for infectious causes of human cancers: where and why. Virology. 2009;392:1–10.
Kuppers R. B cells under influence: transformation of b cells by Epstein–Barr virus. Nat Rev Immunol. 2003;3:801–12.
Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10:789–99.
Vogelstein B, Kinzler KW. The multistep nature of cancer. Trends Genet. 1993;9:138–41.
Hurme M. Is susceptibility to infections in the genes? Duodecim. 1998;114:733–4.
Wang JM, Deng X, Gong W, Su S. Chemokines and their role in tumor growth and metastasis. J Immunol Methods. 1998;220:1–17.
Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer. 2004;4:11–22.
Kroeger KM, Carville KS, Abraham LJ. The −308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol. 1997;34:391–9.
Kroeger KM, Steer JH, Joyce DA, Abraham LJ. Effects of stimulus and cell type on the expression of the −308 tumour necrosis factor promoter polymorphism. Cytokine. 2000;12:110–9.
Brinkman BM, Zuijdeest D, Kaijzel EL, Breedveld FC, Verweij CL. Relevance of the tumor necrosis factor alpha (TNF alpha) −308 promoter polymorphism in TNF alpha gene regulation. J Inflamm. 1995;46:32–41.
Wilson AG, di Giovine FS, Duff GW. Genetics of tumour necrosis factor-alpha in autoimmune, infectious, and neoplastic diseases. J Inflamm. 1995;45:1–12.
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997;94:3195–9.
Nedospasov SA, Udalova IA, Kuprash DV, Turetskaya RL. DNA sequence polymorphism at the human tumor necrosis factor (TNF) locus. Numerous TNF/lymphotoxin alleles tagged by two closely linked microsatellites in the upstream region of the lymphotoxin (TNF-beta) gene. J Immunol. 1991;147:1053–9.
Canedo P, Duraes C, Pereira F, Regalo G, Lunet N, Barros H, et al. Tumor necrosis factor alpha extended haplotypes and risk of gastric carcinoma. Cancer Epidemiol Biomarkers Prev. 2008;17:2416–20.
Duarte I, Santos A, Sousa H, Catarino R, Pinto D, Matos A, et al. G-308A TNF-alpha polymorphism is associated with an increased risk of invasive cervical cancer. Biochem Biophys Res Commun. 2005;334:588–92.
Ho SY, Wang YJ, Chen HL, Chen CH, Chang CJ, Wang PJ, et al. Increased risk of developing hepatocellular carcinoma associated with carriage of the TNF2 allele of the −308 tumor necrosis factor-alpha promoter gene. Cancer Causes Control. 2004;15:657–63.
Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, et al. A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology. 2003;125:364–71.
Peleteiro B, Lunet N, Carrilho C, Duraes C, Machado JC, La Vecchia C, et al. Association between cytokine gene polymorphisms and gastric precancerous lesions: systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010;19:762–76.
Sousa H, Breda E, Santos AM, Catarino R, Pinto D, Medeiros R. Genetic risk markers for nasopharyngeal carcinoma in portugal: tumor necrosis factor alpha −308G > A polymorphism. DNA Cell Biol. 2011;30:99–103.
Zhang HL, Zhang YJ. A systemic assessment of the association between tumor necrosis factor alpha 308 G/A polymorphism and risk of cervical cancer. Tumour Biol. 2013;34:1659–65.
Siegler G, Meyer B, Dawson C, Brachtel E, Lennerz J, Koch C, et al. Expression of tumor necrosis factor receptor-associated factor 1 in nasopharyngeal carcinoma: possible upregulation by Epstein–Barr virus latent membrane protein 1. Int J Cancer. 2004;112:265–72.
Wu MS, Huang SP, Chang YT, Shun CT, Chang MC, Lin MT, et al. Tumor necrosis factor-alpha and interleukin-10 promoter polymorphisms in Epstein–Barr virus-associated gastric carcinoma. J Infect Dis. 2002;185:106–9.
Mullenbach R, Lagoda PJ, Welter C. An efficient salt-chloroform extraction of DNA from blood and tissues. Trends Genet. 1989;5:391.
Bond GL, Levine AJ. A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans. Oncogene. 2007;26:1317–23.
Catarino R, Pereira D, Breda E, Coelho A, Matos A, Lopes C, et al. Oncogenic virus-associated neoplasia: a role for cyclin D1 genotypes influencing the age of onset of disease? Biochem Biophys Res Commun. 2008;370:118–22.
Cardoso CS, Araujo HC, Cruz E, Afonso A, Mascarenhas C, Almeida S, et al. Haemochromatosis gene (HFE) mutations in viral-associated neoplasia: linkage to cervical cancer. Biochem Biophys Res Commun. 2006;341:232–8.
Coelho A, Matos A, Catarino R, Pinto D, Sousa H, Pereira D, et al. The influence of chemokine receptor CCR2 genotypes in the route to cervical carcinogenesis. Gynecol Obstet Invest. 2007;64:208–12.
Costa S, Medeiros R, Vasconcelos A, Pinto D, Lopes C. A slow acetylator genotype associated with an increased risk of advanced cervical cancer. J Cancer Res Clin Oncol. 2002;128:678–82.
Craveiro R, Bravo I, Catarino R, Teixeira AL, Sousa H, Pereira D, et al. The role of p73 G4C14-to-A4T14 polymorphism in the susceptibility to cervical cancer. DNA Cell Biol. 2012;31:224–9.
Santos AM, Sousa H, Catarino R, Pinto D, Pereira D, Vasconcelos A, et al. TP53 codon 72 polymorphism and risk for cervical cancer in Portugal. Cancer Genet Cytogenet. 2005;159:143–7.
Sousa H, Santos AM, Catarino R, Pinto D, Moutinho J, Canedo P, et al. IL-1RN VNTR polymorphism and genetic susceptibility to cervical cancer in Portugal. Mol Biol Rep. 2012;39:10837–42.
Pillai S, Bikle DD, Eessalu TE, Aggarwal BB, Elias PM. Binding and biological effects of tumor necrosis factor alpha on cultured human neonatal foreskin keratinocytes. J Clin Invest. 1989;83:816–21.
Eksteen JA, Scott PA, Perry I, Jankowski JA. Inflammation promotes Barrett’s metaplasia and cancer: a unique role for TNFalpha. Eur J Cancer Prev. 2001;10:163–6.
Stuber F, Udalova IA, Book M, Drutskaya LN, Kuprash DV, Turetskaya RL, et al. 308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter. J Inflamm. 1995;46:42–50.
Frazer IH. Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol. 2004;4:46–54.
Wilson AG, Duff GW. Tumor necrosis factor. Lancet. 1995;345:649.
Acknowledgments
This study was performed as part of the Doctoral Degree of the first author which was awarded with an individual grant for Doctoral degree by Fundação para a Ciência e Tecnologia (SFRH/BD/40718/2007). Authors also would like to acknowledge to the Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro—Núcleo Regional do Norte) for the support to the Molecular Oncology Group.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Additional information
José Moutinho (MD) is actually retired from the institution, but at the date of study development, he was responsible for patient selection.
Rights and permissions
About this article
Cite this article
Sousa, H., Oliveira, S., Santos, A.M. et al. Tumour necrosis factor alpha 308 G/A is a risk marker for the progression from high-grade lesions to invasive cervical cancer. Tumor Biol. 35, 2561–2564 (2014). https://doi.org/10.1007/s13277-013-1337-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-013-1337-3