title: Relationships between Common and Novel Interleukin-6 Gene Polymorphisms and Risk of Cervical Cancer: a Case-Control Study.
abstract: We investigated the association between six common and novel interleukin-6 (IL-6) polymorphisms with the risk of cervical cancer (CC) among Tunisians. Study subjects comprised 112 CC cases and 164 control women. Genotyping of IL-6 rs2069845, rs2069840, rs1474348, rs1800795, rs1800797, rs2069827 variants was done by real-time PCR, with defined clusters. The allelic and genotypic distributions of the tested IL-6 SNPs were comparable between CC patients and control women. Stratification according to FIGO staging revealed that rs1800795 homozygous major allele genotype (P = 0.033; OR =0.49(0.25-0.95)) and major allele (P = 0.037; OR = 0.57 (0.33-0.97)) were protective of CC. Moreover, carriage of rs1474348 major allele was also protective of CC (P = 0.014; OR = 0.53(0.32-0.88)), while higher rs1474348 minor allele frequency was seen in CC patients with early FIGO stage (P = 0.044; OR = 0.39 (0.15-1.00)), thus implicating rs1474348 in CC evolution and progression of angiogenesis. Haploview analysis demonstrated high linkage disequilibrium (LD) between rs2069845, rs2069840, rs1474348 and rs1800795, and 6-locus haplotype analysis identified GACCCA haplotype to be positively associated with increased CC, while GAGGGG haplotype was negatively associated with CC, thus suggesting a protective role for this haplotype in CC. Furthermore, there was a significant association between the incidence of CC and the use hormonal contraception (P = 0.047; OR = 1.97 (0.94-4.13)) and smoking (P < 0.001; OR = 7.12 (2.97-17.04)). The IL-6 variants rs1800795 and rs1474348, and haplotypes GACCCA and GAGGGG, along with use of hormonal contraceptives and smoking, are major risk factors of CC susceptibility and evolution among Tunisian women.
authors.affiliation: Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, El Manar University, 1092, Tunis, Tunisia. ZIDISABRINA86@gmail.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Zidi
authors.affiliation: Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, El Manar University, 1092, Tunis, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Stayoussef
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Bano L
authors.initials: BL
authors.lastname: Alsaleh
authors.affiliation: Military Hospital of Tunis, Laboratory of Immunology, Tunis, Tunisia.
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Gazouani
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: Bashayer H
authors.initials: BH
authors.lastname: Ebrahim
authors.affiliation: Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, El Manar University, 1092, Tunis, Tunisia.
authors.forename: Besma
authors.initials: B
authors.lastname: Yacoubi-Loueslati
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Cervical cancer; FIGO stages; Haplotypes; Interleukin-6; Polymorphisms; Tunisians