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Zidi S.,Tunis el Manar University | Stayoussef M.,University of Monastir | Zouidi F.,University of Sfax | Benali S.,Tunis el Manar University | And 3 more authors.
Pathology and Oncology Research | Year: 2015

Host genetic factors may confer susceptibility to Cervical Cancer. TNF-α as pro-inflammatory cytokine participates in the maintenance of immune homeostasis. Allelic variation of immuno-modulatory genes is associated with alteration in immune function. This study investigated the associations between TNF-α-308G>A, −238G>A, and TNFRII - VNTR-322 and cervical cancer in Tunisian women. Genotypes of those polymorphisms were detected in 130 cases and 260 controls. The variant heterozygote −308 G/A was associated with a 41 % decreased risk of cervical cancer (GG vs A/A; p = 0.002; OR = 0.41; 95 % CI =0.23–0.76). Furthermore, compared with dominant variant G/G, the (G/A+A/A) genotypes was significantly associated with a decreased risk of CC (GG vs G/A+A/A; p = 0.026; OR = 0.62; 95 % CI = 0.40–0.97). The FIGO stratified analysis showed that the minor variant A/A and combined G/A+A/A of TNFα-238 G>A and TNFα-308 G>A increased the risk of the tumor evolution, respectively, (P = 0.011; OR = 2.98; 95 % CI = 1.16–7.72) (P = 0.008; OR = 2.76; 95 % CI = 1.20–6.41), (P = 0.000; OR = 16.33; 95 % CI = (5.10–55.23) (P = 0.000; OR = 7.54; 95 % CI = 2.68–22.29). There was statistically significant relationship between the incidence of the TNF-α mutations and the clinical progression of cancer according to the FIGO classification. In our study, the haploview analysis revealed no LD between rs1800629 and rs361525. TNF-α and TNFRII polymorphisms might be genetic risk factors for cervical cancer inTunisian population © 2014, Arányi Lajos Foundation.


Makni L.,Tunis el Manar University | Stayoussef M.,University of Monastir | Ghazouani E.,Laboratory of Immunology | Mezlini A.,Salah Azeiz Oncology Institute | And 2 more authors.
Meta Gene | Year: 2016

Background: We evaluated the association of common VEGF-A SNPs as potential risk factors for laryngeal cancer (LC) and nasopharyngeal carcinoma (NPC) in Tunisians. Methods: Study subjects comprised 73 NPC and 48 LC patients, along with 125 cancer-free control subjects. VEGF-A genotyping was done by the allelic discrimination method. Results: Minor allele frequency (MAF) of the 8 tested VEGF-A SNPs was comparable between LC patients and controls. Significantly higher MAF of rs2010963 and rs833070 were seen in NPC patients compared to controls. Increased nasopharyngeal cancer risk was seen with both rs2010963 and rs833070 as heterozygous, and more so as homozygous states, thus establishing a dose-dependent effect. In addition, increased NPC risk was associated with rs833068 only in heterozygous state. Increased frequency of CCGAACTC haplotype was seen in LC cases than controls. This was in sharp contrast to NPC, where highly significant positive association was seen with ATCGGCCC, ATGAGCCC, CCCAGTCC, and CCGAACCC haplotypes, while ATCAACCC, ATGGACCC, CCCAGCCC, CCCAGCCT, and ATGGATCC haplotypes are protective factors for NPC. Conclusion: VEGF-A SNPs are associated with altered risk of NPC, but not with LC, among Tunisian subjects. © 2016 The Authors.


Zidi S.,Tunis el Manar University | Verdi H.,Baskent University | Yilmaz-Yalcin Y.,Baskent University | Yazici A.C.,Baskent University | And 4 more authors.
Pathology & Oncology Research | Year: 2014

Accumulative epidemiological evidence suggests that polymorphisms of cytokine genes and Toll-like receptors (TLR) signaling pathway elucidated the cellular and molecular mechanisms of human diseases, including cervical cancer, whose gaining a primordial importance. The aim of our study was to identify the role of TLR 2 (-196 to -174 del), TLR 3 (1377 C > T), TLR 4 (Asp299Gly), TLR 9 (G2848A), IL1-α (4845 G > T), IL-1β (-511C > T) and TNF-α (-238 G > A) gene polymorphisms with cervical cancer susceptibility in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer (n = 130) and unrelated healthy female controls of similar ethnicity (n = 200). Genomic DNA was extracted from peripheral blood leukocytes using QIAamp® DNA blood Mini Kit method. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR3 (1377 C > T) polymorphism, the OR for patients with C/T vs C/C genotype was 2.00 (95 % CI: 1.22-3.31; p = 0.0036) and the OR of C/T + T/T vs C/C genotype was 1.85 (95 % CI: 1.15-2.96; p = 0.0070). For TLR4 (Asp299Gly), the Asp allele and Asp/Asp genotype are associated with higher risk of developing CC: the allelic comparison Asp vs Gly was (OR: 5.70, 95 % CI: 3.44-9.52), for the genotypic comparison Asp/Asp vs Asp/Gly, vs Gly/Gly and vs Asp/Gly + Gly/Gly was respectively; (OR: 11.99, 95%CI: 4.73-32.21) (OR: 5.51, 95 % CI: 2.33-13.47) and (OR: 8.29, 95 % CI: 4.30-16.20) . For IL-1β (-511), the OR for patients with T/T vs C/C genotype was 5.33 (95 % CI: 2.15-13.45; p = 0.0000) and the OR of combined C/T + T/T vs C/C genotype was 1.77 (95 % CI: 0.98-3.22; p = 0.0430). Our study suggests that the TLR3 (1377 C > T), TLR4 (Asp299Gly), and IL-1β (-511C > T) polymorphisms may be a genetic risk factor for cervical cancer. © 2014 Arányi Lajos Foundation.


Zidi S.,Tunis el Manar University | Sghaier I.,Tunis el Manar University | Zouidi F.,CHU HABIB BOURGUIBA Sfax | Benahmed A.,Tunis el Manar University | And 5 more authors.
Pathology and Oncology Research | Year: 2015

Our study aimed to evaluate the association between IL-1α (4845 G/T), IL-1β (-511C/T) and IL-1RN (VNTR) polymorphisms and risk of cervical cancer. This case-control study investigates three polymorphisms in 130 patients and 260 controls by PCR-restriction fragment length polymorphism (RFLP). The IL-1RN (VNTR) A1/A3 genotype appear as a cervical cancer risk factor (p = 0.048; OR = 2.92; 95 % CI = 1.00–8.74), moreover, the L/2* decreased the risk (p = 0.011; OR = 0.47; 95 % CI = 0.25–0.88) and may be a protective factor against this pathology. Stratified analysis according to the FIGO stage subgroup revealed that the IL-1β-511 T/T genotype and T allele may be a protective factors against cervical cancer development for patients with early stage (p = 0.030; OR = 0.46; 95 % CI = 0.22–0.96) (p = 0.020; OR = 0.68; 95 % CI = 0.48–0.97). However, for the patients with advanced FIGO stage, IL-1RN-VNTR L/2* genotype appear as a protective factor for this pathology (p = 0.023; OR = 0.29; 95 % CI = 0.08–0.99). The (G-T-L) haplotype showed a significant decreased frequency in cervical cancer patients as compared to controls (p = 0.032; OR = 0.53; 95 % CI = 0.29–0.95). In contrast, the (T-T-2*) combination appear a risk factor for the development of cervical cancer (p = 0.018; OR = 1.57; 95 % CI = 1.07–2.30). Our study suggested that IL1 cluster polymorphisms and haplotypes may be a genetic risk factor for cervical cancer. © 2015, Arányi Lajos Foundation.


Zidi S.,Tunis el Manar University | Sghaier I.,Tunis el Manar University | Gazouani E.,Laboratory of Immunology | Mezlini A.,Salah Azeiz Oncology Institute | Yacoubi-Loueslati B.,Tunis el Manar University
Pathology and Oncology Research | Year: 2015

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 versuss 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. © 2015 Arányi Lajos Foundation

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