title: TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals.
abstract: Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Instituto do Fígado de Pernambuco (IFP), Recife, Brasil.|Faculdade de Ciências Médicas (FCM), Universidade de Pernambuco (UPE), Recife, Brasil.
authors.forename: Dayse Celia
authors.initials: DC
authors.lastname: Aroucha
authors.affiliation: Colegiado de Farmácia, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina, Brasil.|Rede Nordeste de Biotecnologia (RENORBIO), Recife, Brasil.
authors.forename: Rodrigo Feliciano
authors.initials: RF
authors.lastname: Carmo
authors.affiliation: Instituto do Fígado de Pernambuco (IFP), Recife, Brasil.|Departamento de Parasitologia, Centro de Pesquisas Aggeu Magalhães (CPqAM), Fundação Oswaldo Cruz (FIOCRUZ), Recife, Brasil.
authors.forename: Luydson Richardson Silva
authors.initials: LR
authors.lastname: Vasconcelos
authors.affiliation: Instituto de Ciências Biológicas (ICB), Universidade de Pernambuco (UPE), Recife, Brasil.
authors.forename: Raul Emidio
authors.initials: RE
authors.lastname: Lima
authors.affiliation: Rede Nordeste de Biotecnologia (RENORBIO), Recife, Brasil.
authors.forename: Taciana Furtado
authors.initials: TF
authors.lastname: Mendonça
authors.affiliation: Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brasil.
authors.forename: Lucia Elena
authors.initials: LE
authors.lastname: Arnez
authors.affiliation: Instituto de Ciências Biológicas (ICB), Universidade de Pernambuco (UPE), Recife, Brasil.
authors.forename: Maria do Socorro Mendonça
authors.initials: Mdo S
authors.lastname: Cavalcanti
authors.affiliation: Instituto de Ciências Biológicas (ICB), Universidade de Pernambuco (UPE), Recife, Brasil.
authors.forename: Maria Tereza Cartaxo
authors.initials: MT
authors.lastname: Muniz
authors.affiliation: Centro de Ciências da Saúde (CCS), Universidade Federal de Pernambuco (UFPE), Brazil.
authors.forename: Marcilio Lins
authors.initials: ML
authors.lastname: Aroucha
authors.affiliation: Instituto do Fígado de Pernambuco (IFP), Recife, Brasil.
authors.forename: Erika Rabelo
authors.initials: ER
authors.lastname: Siqueira
authors.affiliation: Instituto do Fígado de Pernambuco (IFP), Recife, Brasil.
authors.forename: Luciano Beltrão
authors.initials: LB
authors.lastname: Pereira
authors.affiliation: Instituto de Ciências Biológicas (ICB), Universidade de Pernambuco (UPE), Recife, Brasil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Moura
authors.affiliation: Instituto do Fígado de Pernambuco (IFP), Recife, Brasil.|Faculdade de Ciências Médicas (FCM), Universidade de Pernambuco (UPE), Recife, Brasil.
authors.forename: Leila Maria Moreira Beltrão
authors.initials: LM
authors.lastname: Pereira
authors.affiliation: Setor de Virologia do Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE), Brazil.
authors.forename: Maria Rosangela
authors.initials: MR
authors.lastname: Coêlho
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C508609:IL10 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: cytokines; hepatitis c virus; inflammation; interleukin