Contribution of Nitric oxide synthase 3 genetic variants to nasopharyngeal carcinoma risk and progression in a Tunisian population

  • Sahar Aouf
  • Ala Laribi
  • Sallouha Gabbouj
  • Elham Hassen
  • Noureddine Bouaouinaa
  • Abdelfattah Zakhama
  • Hedi HariziEmail author
Head & Neck



We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population.


259 NPC patients and 169 healthy controls were enrolled into our case–control study. Blood samples were genotyped by the RFLP-PCR analysis. The levels of Nitric oxide (NO) were measured by a colorimetric assay kit in the plasma of NPC patients, healthy controls and according to NOS3 genotypes. The correlation between the NOS3 variants and the clinicopathological parameters was examined.


We found no linkage disequilibrium between NOS3 T-786C and G894T variants. These results showed that NOS3 variants were genetically independent. In contrast to NOS3 T-786C, a significant association was found between NOS3 G894T polymorphism and NPC risk. The 894T allele decreased significantly in NPC patients and appeared as protective factor (OR = 0.65, CI 95%= 0.48–0.88, p = 0.006). NPC patients had significantly higher levels of plasma NO as compared to healthy controls (p = 0.0011). The T-786C mutation reduced the levels of plasma NO and decreased risk of lymph node metastasis in NPC patients (OR = 0.64, 95% CI = 0.43–0.96; p = 0.03). In contrast, NOS3 G894T polymorphism had no effects neither on NO plasma levels nor clinical parameters.


This is the first study to associate NPC with significantly higher levels of plasma NO. NOS3-derived NO could play key roles in NPC pathogenesis. NOS3 variants differently contribute to NPC risk and progression in a Tunisian population. NOS3 G894T was associated with NPC risk. NOS3 T-786C decreased the levels of plasma NO and reduced the development of regional lymph node metastasis.


NOS3 gene Polymorphisms Plasma NO Nasopharyngeal carcinoma Clinical parameters 



This study was supported by the Ministry of Higher Education and Scientific Research and by the Ministry of Health of the Republic of Tunisia. The authors would like to thank Dr. Samir Bougattaya for proof-reading the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Molecular Immuno-Oncology, Faculty of Medicine of MonastirUniversity of MonastirMonastirTunisia
  2. 2.Department of Cancerology and RadiotherapyFarhat Hached University HospitalMonastirTunisia
  3. 3.Department of Anatomy and Pathologic CytologyFattouma Bourguiba University HospitalMonastirTunisia
  4. 4.Faculty of Dental MedicineUniversity of MonastirMonastirTunisia

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