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.

Susceptibility to HIV‐1 infection is influenced by toll like receptor‐2 (−196 to −174) polymorphism in a north Indian population

“…evaluated the role of TLR2 in periodontal disease in an HIV positive North American cohort and found it to be associated with bleeding on probing, an indicator of an subgingival inflammatory response to bacterial pathogens. The results of the present study are also consistent with previous studies conducted in Indian and other Asian population showing that the TLR2 Ins/Del polymorphism is associated with the risk of severe malaria, cervical cancer, gallbladder cancer, prostate cancer, Epstein–Barr virus associated gastric carcinoma in Chinese and tuberculosis …”

“…29 It was also found to be associated with tuberculosis in Caucasians and Africans, 30 colorectal cancer in Brazilians, 31 in breast cancer 32 and in Parkinson 0 s disease in a Greek population. 33 Asian population showing that the TLR2 Ins/Del polymorphism is associated with the risk of severe malaria, 35 cervical cancer, 36,37 gallbladder cancer, 38 prostate cancer, 17,39 Epstein-Barr virus associated gastric carcinoma in Chinese 40,41 and tuberculosis. 42 The three nonsynonymous polymorphisms in the TLR2 gene (Arg753Gyn, Arg677Trp and Pro631His) are associated with altered TLR2 signaling and have been reported to influence susceptibility to various infections.…”

-196 to -174del, rs4696480, rs3804099 polymorphisms of Toll-like receptor 2 gene impact the susceptibility of cancers: evidence from 37053 subjects

“…The results of pooled analysis for TLR2 polymorphism and cancer susceptibility are provided in Table 2 . For -196 to -174del, we collected 18 articles containing 3943 cases and 4574 controls [1][2][3]6,[8][9][10][11][12][28][29][30][31][32][33][34][35][36]. In the overall analysis, -196 to -174del significantly increased the risk of cancer [B vs. A (OR = 1.468, 95% Cl = 1.129-1.91, P=0.005); BB vs. AA (OR = 1.716, 95% Cl = 1.178-2.5, P=0.005); BA vs. AA (OR = 1.408, 95% Cl = 1.092-1.816, P=0.008); BB+BA vs. AA (OR = 1.449, 95% Cl = 1.107-1.897, P=0.007); BB vs. BA+AA (OR = 1.517, 95% Cl = 1.092-2.107, P=0.013)] ( Figure 2).…”

Toll-Like Receptors Gene Polymorphism and Susceptibility to Cancer Development

“…Otherwise, investigation of TLR3 rs5743305 and rs3775291 polymorphisms has shown no significant correlation between these SNPs and the risk of cervical cancer, among a Swedish population [49]. Among North Indian population, Pandey et al found no association between rs3775290 TLR3 polymorphism and cervical cancer development [50], while Zidi et al found that rs3775290 TLR3 polymorphism (+1377 C > T genotype) increased the risk of cervical cancer in advantage stages [40].…”