Impact of toll-like receptor 4 variations on nasopharyngeal carcinoma risk and survival in tunisian population

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Published Feb 18, 2024
https://doi.org/10.62438/tunismed.v102i2.4270
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Vol. 102 No. 2 (2024): Tunis med feb 2024

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Arij Ben Chaaben
Humain genetic Lab, Medical school of Tunis, Tunis El Manar University, Clinical Biology Lab, Salah Azaiz Institute, High School of Sciences and Techniques of Health, Tunis El Manar University, Tunisia
Imen Ayadi
Immunology Laboratory, La Rabta Hospital, Tunis, Tunisia
Hejer Abaza
Humain genetic Lab, Medical school of Tunis, Tunis El Manar University, Clinical Biology Lab, Salah Azaiz Institute, Tunisia
Olfa Baroudi
Humain genetic Lab, Medical school of Tunis, Tunis El Manar University, Tunisia
Hayet Douik
Humain genetic Lab, Medical school of Tunis, Tunis El Manar University, Clinical Biology Lab, Salah Azaiz Institute, Tunisia
Latifa Harzallah
Clinical Biology Lab, Salah Azaiz Institute, Tunisia
Jihen Bouassida
Univ Paris Est Créteil, INSERM, IMRB,Translational Neuropsychiatry, AP-HP, DMU IMPACT, FHU ADAPT, Fondation FondaMental, Créteil, France.
Wahid Bouckouaci
Univ Paris Est Créteil, INSERM, IMRB,Translational Neuropsychiatry, AP-HP, DMU IMPACT, FHU ADAPT, Fondation FondaMental, INSERM UMRS 940 and “Assistance Publique des Hôpitaux de Paris (AP-HP)” Créteil, France.
Fethi Guemira
Clinical Biology Laboratory, Salah Azaiz Institute, Tunisia
Amani Mankai
High School of Sciences and Techniques of Health, Tunis El Manar University, Tunis,Tunisia
Maher Kharrat
Humain genetic Laboratory, Medical school of Tunis, Tunis El Manar University, Tunisia
Ryad Tamouza
Univ Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, AP-HP, DMU IMPACT, FHU ADAPT, Fondation FondaMental, INSERM UMRS 940 and “Assistance Publique des Hôpitaux de Paris (AP-HP)”Créteil, France

Abstract

Introduction: The Toll-like receptor 4 (TLR4), an important member of the host's innate immune response, is coded by a polymorphic gene. This polymorphism could be a predisposing factor for NasoPharyngeal Carcinoma (NPC).


Aim: To determine the association between TLR4 gene polymorphisms and the susceptibility to NPC in a cohort of Tunisian affected patients.


Methods: Genomic DNAs from 245 unrelated patients affected by undifferentiated carcinoma type (UCNT) and 264 unrelated healthy controls were genotyped for the five single nucleotides polymorphisms (SNPs) of TLR4 locus (4434 A>G (rs1927914),7263 G>C (rs10759932), 6134 A>G(rs4986790), 8851C>T (rs 4986791), 5272 T>C(rs11536889), +8469 T>C (rs11536891)) by Taqman® 5’-nuclease assay.


Results: Among all polymorphisms studied, only the rs4986790 G and rs4986791 T alleles were significantly more prevalent in patients’ group than controls (45% vs. 38%; p=0.03; pc=0.06) and increased the risk of the NPC (OR=1.3, 95% CI=1.01-1.69).  Also, we found that the frequency of the rs4986790 AA and rs4986791 TT genotypes was significantly higher in controls than in patients (25.7% vs 37%; p=0.006, pc=0.02) and conferred a protector factor in NPC (OR= 0.59, 95% CI= 0.39-0.87). Further, based on the Kaplan-Meier survival curve we observed also the positive effect ofrs1927914 AA genotype on a prognostic of NPC (p=0.006; pc=0.01).


Conclusion: Our study demonstrated that impaired production of TLR4 seems to be a risk factor of NPC development but functional studies are needed to confirm these findings. As to rs1927914 AA appears to be a good biomarker for better survival in a patient with NPC.

Keywords:

Nasopharyngeal carcinoma, TLR4, gene, polymorphism, risk

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