Zidi Sabrina, Sghaier Ikram, Gazouani Ezzedine, Mezlini Amel, Yacoubi-Loueslati Besma
Faculty of Sciences of Tunis, Laboratory of Micro-Organisms and Active Biomolecules, El Manar University, 2092 El MANAR I, 1092, Tunis, Tunisia.
Laboratory of Immunology, Military Hospital of Tunis, Tunis, Tunisia.
Pathol Oncol Res. 2016 Apr;22(2):323-30. doi: 10.1007/s12253-015-0009-6. Epub 2015 Nov 9.
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.
累积的流行病学证据表明，Toll样受体信号通路的多态性阐明了人类疾病的细胞和分子机制，这些机制正变得至关重要。我们研究的目的是确定TLR 2（-196至-174缺失）、TLR 3（1377 C>T）、TLR 4（Asp299Gly）和TLR 9（G2848A）基因多态性与突尼斯女性宫颈癌进展之间的关系。从经组织病理学确诊的宫颈癌患者和种族相似的无关健康女性对照中采集血样。使用聚合酶链反应和限制性片段长度多态性对分析的多态性进行基因分型。对于TLR 2，Ins/Ins基因型是一个保护因素[p = 0.006；OR：0.35（0.16 - 0.73）]，TLR 3的显性基因型增加了（III + IV）期宫颈癌的风险；C/C与C/T相比[p = 0.033；OR：2.03（1.00 - 4.13）]以及C/C与C/T + T/T相比[p = 0.036；OR：1.93（1.00 - 3.74）]。对于TLR 4，显性基因型Asp/Asp与（I + II）期宫颈癌的发生有关[p = 0.000；OR：4.55（1.58 - 13.06）]，[p = 0.001；OR：3.49（1.44 - 8.45）]以及（III + IV）期[p = 0.038；OR：3.77（0.87 - 16.29）]，[p = 0.007；OR：5.21（1.65 - 16.46）]，并且主要等位基因Asp是（I + II）期肿瘤发生的危险因素。TLR2 Ins/Del基因型与肿瘤进展至（III + IV）期有关[p = 0.003；OR：3.00（1.22 - 7.35）]，TLR 4的Gly/Gly和Asp/Gly + Gly/Gly基因型以及Gly等位基因与肿瘤进展至晚期有关。此外，TLR 2、TLR 3、TLR 4和TLR 9基因多态性与病例中因吸烟和绝经状态导致的宫颈癌风险调节有关。我们的研究表明，根据国际妇产科联盟（FIGO）分类，TLR2、TLR 3、TLR 4和TLR9突变的发生率与宫颈癌的临床进展之间存在关联。然而，未来在不同种族人群中进行的具有不同人口统计学和临床特征的研究可能会更全面地揭示先天性免疫在全球女性宫颈癌病因中的作用。
