title: Tumor necrosis factor (TNF) alpha and interleukin (IL) 18 genes polymorphisms are correlated with susceptibility to HPV infection in patients with and without cervical intraepithelial lesion.
abstract: BACKGROUND
  The Human Papillomavirus (HPV) predisposes 500 000 women to cervical cancer. Host genetic background may facilitate virus persistence in the uterine cervix. Polymorphisms in regulatory and coding regions of cytokine genes have been associated with susceptibility to some human diseases.
  
  
  OBJECTIVE
  This study aims at investigating whether TNFA -308 G/A and IL18 -137 G/C and -607 C/A polymorphisms are associated with susceptibility to HPV infection/progression to high-grade squamous intraepithelial lesion (HSIL).
  
  
  METHODS
  One hundred and twenty-two HPV infected and 132 HPV negative women (the latter used as healthy controls) were analysed. TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were analysed using specific sequence polymorphism PCR (SSP-PCR). Univariate statistical analysis and a logistic regression were performed.
  
  
  RESULTS
  The TNFA -308A allele was associated with susceptibility to HPV infection (p = 0.0008), while the IL18 -607A allele conferred protection against HPV infection (p = 0.0043). TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were not associated with development of cervical lesions (p > 0.05). An association was also observed between smoking and susceptibility to the development of HSIL.
  
  
  CONCLUSIONS
  The findings suggest an association between two TNFA SNPs and susceptibility to HPV infection in women from Northeast Brazil. The results need to be functionally validated and replicated in other populations with different ethnic backgrounds.
authors.affiliation: a Applied Molecular Biology .
authors.forename: Mayara C Mansur
authors.initials: MC
authors.lastname: Tavares
authors.affiliation: a Applied Molecular Biology .
authors.forename: Sérgio F
authors.initials: SF
authors.lastname: de Lima Júnior
authors.affiliation: b Department of Genetics , Universidade Federal de Pernambuco (UFPE) , Recife , PE , Brazil .
authors.forename: Antonio V C
authors.initials: AV
authors.lastname: Coelho
authors.affiliation: c Biology Sciences, Universidade Federal Rural de Pernambuco (UFRPE) , Recife , PE , Brazil .
authors.forename: Trícia Ruschelle N M
authors.initials: TR
authors.lastname: Marques
authors.affiliation: c Biology Sciences, Universidade Federal Rural de Pernambuco (UFRPE) , Recife , PE , Brazil .
authors.forename: Diêgo Henrique T
authors.initials: DH
authors.lastname: de Araújo
authors.affiliation: d Departament of Lower Genital Tract Pathology , Women's Healthcare Center .
authors.forename: Sandra de A
authors.initials: Sde A
authors.lastname: Heráclio
authors.affiliation: e Maternal and Child Healthcare Departament, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) , Recife , PE , Brazil , and.
authors.forename: Melânia M Ramos
authors.initials: MM
authors.lastname: Amorim
authors.affiliation: f Biology Department , Universidade Federal Rural de Pernambuco (UFRPE) , Recife , PE , Brazil.
authors.forename: Paulo Roberto E
authors.initials: PR
authors.lastname: de Souza
authors.affiliation: b Department of Genetics , Universidade Federal de Pernambuco (UFPE) , Recife , PE , Brazil .
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008875:Middle Aged; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology
chemical_list: D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha
keywords: Cytokine; invasive cervical cancer; single nucleotide polymorphism