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Journal of Cancer Research and Clinical Oncology

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01-08-2020 | Human Papillomavirus | Original Article – Cancer Research

IL-10 c.-592C>A (rs1800872) polymorphism is associated with cervical cancer

Authors: Ana Paula Lombardi Pereira, Kleber Paiva Trugilo, Nádia Calvo Martins Okuyama, Michelle Mota Sena, José D’Oliveira Couto-filho, Maria Angelica Ehara Watanabe, Karen Brajão de Oliveira

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2020

Abstract

Purpose

Interleukin-10 (IL-10) is an immunoregulatory cytokine and its cervical and serum concentrations have been associated with a poor prognosis of cervical cancer. The rs1800872 polymorphism (c.-592C>A) in the promotor region of the IL-10 gene affects the production and expression of IL-10 and thus is able to determine the immune response profile in the cervix. Therefore, the aim of this work is to state the association between IL-10 c.-592C>A polymorphism and cervical cancer.

Methods

Genomic DNA was extracted from patient’s peripheral blood and tumor biopsy. Socio-demographic, sexual behavior and reproductive characteristics data were collected using a questionnaire.

Results

Co-dominant model in logistic binary regression adjusted for confounders, showed that patients presenting with C/A genotype had 2.15 times more chances for developing cervical cancer (OR 2.15; CI_95% 1.02–4.56). The dominant model, C/A + A/A, was also independently associated with 2.71 times more chances for cervical cancer development when compared to control patients (OR 2.71; CI_95% 1.05–4.47).

Conclusion

Our study analyses show the association between cervical cancer and IL-10 c.-592C>A polymorphism, demonstrating that the allele A presence was independently associated with higher risks of cervical cancer development.

Appleby P, Beral V, Berrington De González A et al (2006) Carcinoma of the cervix and tobacco smoking: collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer 118:1481–1495. https://doi.org/10.1002/ijc.21493 CrossRefPubMed

Bai CY, Shi XY, He J et al (2016) Association between IL-10 genetic variations and cervical cancer susceptibility in a Chinese population. Genet Mol Res 15:2–7. https://doi.org/10.4238/gmr.15038116 CrossRef

Barbisan G, Pérez LO, Contreras A, Golijow CD (2012) TNF-α and IL-10 promoter polymorphisms, HPV infection, and cervical cancer risk. Tumor Biol 33:1549–1556. https://doi.org/10.1007/s13277-012-0408-1 CrossRef

Bauer HM, Ting Y, Greer CE et al (1991) Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA 265:472–477. https://doi.org/10.1001/jama.1991.03460040048027 CrossRefPubMed

Bermudez-Morales VH, Gutierrez LX, Alcocer-Gonzalez JM, Burguete A, Madrid-Marina V (2008) Correlation between IL-10 gene expression and HPV infection in cervical cancer: a mechanism for immune response escape. Cancer Invest 26(10):1037–1043. https://doi.org/10.1080/07357900802112693 CrossRefPubMed

Berti FCB, Pereira APL, Trugilo KP et al (2017) IL-10 gene polymorphism c.-592C%3eA increases HPV infection susceptibility and influences IL-10 levels in HPV infected women. Infect Genet Evol 53:128–134. https://doi.org/10.1016/j.meegid.2017.05.020 CrossRefPubMed

Bhairavabhotla RK, Verm V, Tongaonkar H et al (2007) Role of IL-10 in immune suppression in cervical cancer. Indian J Biochem Biophys 44:350–356PubMed

Capasso M, Avvisati RA, Piscopo C et al (2007) Cytokine gene polymorphisms in Italian preterm infants: association between interleukin-10–1082 G/A polymorphism and respiratory distress syndrome. Pediatr Res 61:313–317. https://doi.org/10.1203/pdr.0b013e318030d108 CrossRefPubMed

Chagas BS, Gurgel APAD, da Cruz HLA et al (2013) An interleukin-10 gene polymorphism associated with the development of cervical lesions in women infected with Human Papillomavirus and using oral contraceptives. Infect Genet Evol 19:32–37. https://doi.org/10.1016/j.meegid.2013.06.016 CrossRefPubMed

Cope A, Le Friec G, Cardone J, Kemper C (2011) The Th1 life cycle: molecular control of IFN-γ to IL-10 switching. Trends Immunol 32:278–286. https://doi.org/10.1016/j.it.2011.03.010 CrossRefPubMed

da Silva MC, Martins HPR, de Souza JL et al (2012) Prevalence of HPV infection and genotypes in women with normal cervical cytology in the state of Paraná, Brazil. Arch Gynecol Obstet 286:1015–1022. https://doi.org/10.1007/s00404-012-2399-y CrossRefPubMed

Du GH, Wang JK, Richards JR, Wang JJ (2019) Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer. Int Immunopharmacol 66:154–161. https://doi.org/10.1016/j.intimp.2018.11.015 CrossRefPubMed

Eldridge RC, Pawlita M, Wilson L et al (2017) Smoking and subsequent human papillomavirus infection: a mediation analysis. Ann Epidemiol 27:724–730.e1. https://doi.org/10.1016/j.annepidem.2017.10.004 CrossRefPubMedPubMedCentral

Guan P, Howell-Jones R, Li N et al (2012) Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 131:2349–2359. https://doi.org/10.1002/ijc.27485 CrossRefPubMed

Hobbs K, Negri J, Klinnert M et al (1998) Interleukin-10 and transforming growth factor-β promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med 158:1958–1962. https://doi.org/10.1164/ajrccm.158.6.9804011 CrossRefPubMed

INCA - Instituto Nacional de Câncer José Alencar Gomes da Silva (2016) Diretrizes Brasileiras para o Rastreamento de Câncer de Colo de Útero. Ministério da Saúde, 2nd edn. Rio de Janeiro, RJ

Insinga RP, Perez G, Wheeler CM et al (2011) Incident cervical HPV infections in young women: transition probabilities for CIN and infection clearance. Cancer Epidemiol Biomark Prev 20:287–296. https://doi.org/10.1158/1055-9965.EPI-10-0791 CrossRef

Ivansson EL, Gustavsson IM, Magnusson JJ et al (2007) Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer. Int J Cancer 121:2451–2457. https://doi.org/10.1002/ijc.22989 CrossRefPubMed

Kessler TA (2017) Cervical cancer: prevention and early detection. Semin Oncol Nurs 33:172–183. https://doi.org/10.1016/j.soncn.2017.02.005 CrossRefPubMed

Kubo M, Motomura Y (2012) Transcriptional regulation of the anti-inflammatory cytokine IL-10 in acquired immune cells. Front Immunol 3:1–9. https://doi.org/10.3389/fimmu.2012.00275 CrossRef

Lees BF, Erickson BK, Huh WK (2016) Cervical cancer screening: evidence behind the guidelines. Am J Obstet Gynecol 214:438–443. https://doi.org/10.1016/j.ajog.2015.10.147 CrossRefPubMed

Mannino MH, Zhu Z, Xiao H et al (2015) The paradoxical role of IL-10 in immunity and cancer. Cancer Lett 367:103–107. https://doi.org/10.1016/j.canlet.2015.07.009 CrossRefPubMed

Mesri EA, Feitelson MA, Munger K (2014) Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe 15:266–282. https://doi.org/10.1016/j.chom.2014.02.011 CrossRefPubMedPubMedCentral

Min Z, Pu X, Gu Z (2018) Correlative analysis of the expression of IL-10 and Ki-67 in human cervical cancer and cervical intraepithelial neoplasias and human papillomavirus infection. Oncol Lett 16:7189–7194. https://doi.org/10.3892/ol.2018.9520 CrossRefPubMedPubMedCentral

Muñoz JP, Carrillo-Beltrán D, Aedo-Aguilera V et al (2018) Tobacco exposure enhances human papillomavirus 16 oncogene expression via EGFR/PI3K/Akt/c-Jun signaling pathway in cervical cancer cells. Front Microbiol 9:1–12. https://doi.org/10.3389/fmicb.2018.03022 CrossRef

Pestka S, Krause CD, Sarkar D et al (2004) Interleukine-10 and related cytokines and receptors. Annu Rev Immunol 22:929–979. https://doi.org/10.1146/annurev.immunol.22.012703.104622 CrossRefPubMed

Reeves G, Sweetland S, Kjaer S et al (2006) Cervical carcinoma and reproductive factors: collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies. Int J Cancer 119:1108–1124. https://doi.org/10.1002/ijc.21953 CrossRef

Rodriguez AC, Schiffman M, Herrero R et al (2008) Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. JNCI J Natl Cancer Inst 100:513–517. https://doi.org/10.1093/jnci/djn044 CrossRefPubMed

Roh JW, Kim MH, Seo SS et al (2002) Interleukin-10 promoter polymorphisms and cervical cancer risk in Korean women. Cancer Lett 184:57–63. https://doi.org/10.1016/S0304-3835(02)00193-3 CrossRefPubMed

Samir R, Asplund A, Tot T et al (2010) Tissue tumor marker expression in smokers, including serum cotinine concentrations, in women with cervical intraepithelial neoplasia or normal squamous cervical epithelium. Am J Obstet Gynecol 202:579.e1–579.e7. https://doi.org/10.1016/j.ajog.2009.11.034 CrossRef

Sasagawa T, Takagi H, Makinoda S (2012) Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer. J Infect Chemother 18:807–815CrossRef

Schiffman M, Castle PEC, Jeronimo J et al (2007) Human papillomavirus and cervical cancer. Lancet 56370:890–970. https://doi.org/10.2222/jsv.56.219 CrossRef

Simen-Kapeu A, Kataja V, Yliskoski M et al (2008) Smoking impairs human papillomavirus (HPV) type 16 and 18 capsids antibody response following natural HPV infection. Scand J Infect Dis 40:745–751. https://doi.org/10.1080/00365540801995360 CrossRefPubMed

Singhal P, Kumar A, Bharadwaj S et al (2015) Association of IL-10 GTC haplotype with serum level and HPV infection in the development of cervical carcinoma. Tumor Biol 36:2287–2298. https://doi.org/10.1007/s13277-014-2836-6 CrossRef

Steinke JW, Barekzi E, Hagman J, Borish L (2004) Functional analysis of −571 IL-10 promoter polymorphism reveals a repressor element controlled by Sp1. J Immunol 173:3215–3222. https://doi.org/10.4049/jimmunol.173.5.3215 CrossRefPubMed

Steinke JW, Barekzi E, Hagman J, Borish L (2014) Functional analysis of −571 IL-10 promoter polymorphism reveals a repressor element controlled by Sp1. J Immunol 173:3215–3222. https://doi.org/10.4049/jimmunol.173.5.3215 CrossRef

Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. https://doi.org/10.3322/caac.21262 CrossRefPubMed

Torres-Poveda K, Burguete-Garcia AI, Cruz M et al (2012) The SNP at -592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development. Infect Agent Cancer 7:32. https://doi.org/10.1186/1750-9378-7-32 CrossRefPubMedPubMedCentral

Torres-Poveda K, Bahena-Román M, Madrid-González C et al (2014) Role of IL-10 and TGF-β1 in local immunosuppression in HPV-associated cervical neoplasia. World J Clin Oncol 5:753–763. https://doi.org/10.5306/wjco.v5.i4.753 CrossRefPubMedPubMedCentral

Turner DM, Williams DM, Sankaran D et al (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8. https://doi.org/10.1111/j.1365-2370.1997.tb00001.x CrossRefPubMed

Wheeler CM, Hunt WC, Joste NE et al (2009) Human Papillomavirus genotype distributions: implications for vaccination and cancer screening in the United States. JNCI J Natl Cancer Inst 101:475–487. https://doi.org/10.1093/jnci/djn510 CrossRefPubMed

WHO - World Health Organization (2016) UN Joint Global Programme on Cervical Cancer Prevention and Control

Zaid A, Hodny Z, Li R, Nelson BD (2001) Sp1 acts as a repressor of the human adenine nucleotide translocase-2 (ANT2) promoter. Eur J Biochem 268:5497–5503. https://doi.org/10.1046/j.1432-1033.2001.02453.x CrossRefPubMed

Zidi S, Gazouani E, Stayoussef M et al (2015) IL-10 gene promoter and intron polymorphisms as genetic biomarkers of cervical cancer susceptibility among Tunisians. Cytokine 76:343–347. https://doi.org/10.1016/j.cyto.2015.05.028 CrossRefPubMed

Zoodsma M, Nolte IM, Schipper M et al (2005) Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease. Int J Gynecol Cancer 15:282–290. https://doi.org/10.1111/j.1525-1438.2005.00433.x CrossRefPubMed

zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350. https://doi.org/10.1038/nrc798 CrossRefPubMed

Title: IL-10 c.-592C>A (rs1800872) polymorphism is associated with cervical cancer
Authors: Ana Paula Lombardi Pereira
Kleber Paiva Trugilo
Nádia Calvo Martins Okuyama
Michelle Mota Sena
José D’Oliveira Couto-filho
Maria Angelica Ehara Watanabe
Karen Brajão de Oliveira
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Human Papillomavirus
Cervical Cancer
Cervical Cancer
Cytokines
Published in: Journal of Cancer Research and Clinical Oncology / Issue 8/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03256-0

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IL-10 c.-592C>A (rs1800872) polymorphism is associated with cervical cancer

Abstract

Purpose

Methods

Results

Conclusion

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Conclusion

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