title: IL-10 gene promoter and intron polymorphisms as genetic biomarkers of cervical cancer susceptibility among Tunisians.
abstract: OBJECTIVE
  We investigated the association between polymorphisms in the promoter and intron regions of the interleukin-10 (IL-10) gene with the risk of cervical cancer (CC) in Tunisian patients and control women.
  
  
  METHODS
  Study subjects comprised 86 CC cases and 126 control women. Genotyping of IL-10 intron (rs3024491, rs3024490) and promoter (rs1800872, rs1800871, rs1800896) variants was done by real-time PCR, with defined clusters.
  
  
  RESULTS
  The minor allele frequencies of the five tested IL-10 SNPs were not significantly different between cervical cancer cases and control women. However, significantly higher frequencies of homozygous minor allele-carriers in cases was seen for rs3024490 (P=0.023), rs1800872 (P=0.037), and rs1800871 (P=0.028). IL-10 serum levels were significantly reduced in rs3024490 T/T vs. G/G genotype carriers, and in rs1800871 T/T than C/C genotype carriers. While carriage of rs1800872 and rs3024491 minor allele was associated with reduced IL-10 secretion, this was not statistically significant. Haploview analysis demonstrated high linkage disequilibrium (LD) among the IL10 SNPs studied, and only seven haplotypes were common, capturing 98.8% of the total possible haplotypes. Reduced frequency of haplotypes GTCCA (P<0.001) and TGATG (P<0.001) was seen in cervical cancer cases than in control women, thus conferring disease protection nature to these haplotype. This association remained significant for GTCCA (Pc=0.006) and TGATG (P=0.045) after correcting for multiple comparisons.
  
  
  CONCLUSIONS
  Specific IL-10 variants (rs3024490, rs1800872, and rs1800871) and haplotype (GTCCA and TGATG) may contribute to the development of cervical cancer among Tunisian women.
authors.affiliation: El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 1092 Tunis, Tunisia.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Zidi
authors.affiliation: Military Hospital of Tunis, Laboratory of Immunology, Tunis, Tunisia.
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Gazouani
authors.affiliation: Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Stayoussef
authors.affiliation: Salah Azeiz Oncology Institute, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Mezlini
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Salma K
authors.initials: SK
authors.lastname: Ahmed
authors.affiliation: El Manar University, Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, 1092 Tunis, Tunisia.
authors.forename: Besma
authors.initials: B
authors.lastname: Yacoubi-Loueslati
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain. Electronic address: wassim@agu.edu.bh.
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007438:Introns; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D014416:Tunisia; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: D015415:Biomarkers; D016753:Interleukin-10
keywords: Cervical cancer; Haplotypes; Interleukin-10; Polymorphisms; Serum levels