title: Evaluation of Toll-Like Receptors 2/3/4/9 Gene Polymorphisms in Cervical Cancer Evolution.
abstract: Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (-196 to -174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16-0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versus C/T [p = 0.033; OR: 2.03(1.00-4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00-3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58-13.06)], [p = 0.001; OR: 3.49(1.44-8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87-16.29)], [p = 0.007; OR: 5.21(1.65-16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22-7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.
authors.affiliation: Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, 2092 El MANAR I, 1092, Tunis, Tunisia. ZIDISABRINA86@gmail.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Zidi
authors.affiliation: Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, 2092 El MANAR I, 1092, Tunis, Tunisia.
authors.forename: Ikram
authors.initials: I
authors.lastname: Sghaier
authors.affiliation: Laboratory of Immunology, Military Hospital of Tunis, 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: Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, 2092 El MANAR I, 1092, Tunis, Tunisia.
authors.forename: Besma
authors.initials: B
authors.lastname: Yacoubi-Loueslati
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051196:Toll-Like Receptor 3 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9
keywords: Cervical cancer; FIGO stage; Gene polymorphism; Toll-like receptor