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Human glutathione peroxidase codon 198 variant increases nasopharyngeal carcinoma risk and progression

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Abstract

Purpose

Glutathione peroxidase 1 (GPx-1) is a selenium-dependent detoxifying enzyme involved in the protection of cells against oxidative damage. Some genetic association studies reported significant associations between GPx-1 Pro198Leu variant and carcinogenesis across different populations; however, the impact of this variant on nasopharyngeal carcinoma (NPC) has not been explored. Therefore, the present study was planned to evaluate the potential involvement of the GPx-1 Pro198Leu variant and plasma GPx activity in the risk of developing NPC in a Tunisian population.

Methods

The GPx-1 Pro198Leu genotype was determined in 327 NPC patients and 150 healthy controls by the RFLP-PCR analysis. The correlation between the GPx-1 variant and the clinicopathological parameters was examined. GPx activity was assessed in the plasma of 119 NPC patients and 58 healthy control subjects and according to GPx-1 genotypes and clinicopathological characteristics of NPC patients.

Results

A significant association was found between GPx-1 Pro198Leu variant and NPC risk in a Tunisian population. The allelic frequencies of Pro and Leu alleles were 32% versus 68% and 41% versus 59% in NPC cases and controls, respectively. Thus, the minor 198 Leu allele increased significantly in NPC patients and appeared as a potential risk factor for NPC occurrence (OR = 1.48, CI 95% = 1.14–1.91, p = 0.002). The plasma GPx activity was significantly higher in NPC patients than in controls (p = 0.03). According to the clinicopathological characteristics of NPC patients, GPx activity decreased significantly in patients with lymph node metastasis (p = 0.004).

Conclusion

This is the first study showing a strong association between GPx-1 Pro198Leu genetic variant and NPC risk. GPx-1 Pro198Leu variant increased the development of regional lymph node metastasis. Plasma GPx activity was higher in NPC patients. Thus, GPx-1 gene could be considered as a determinant factor influencing NPC risk and progression.

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Acknowledgments

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.

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Authors and Affiliations

  1. Laboratory of Molecular Immuno‑Oncology, Faculty of Medicine of Monastir, University of Monastir, 5019, Monastir, Tunisia

    Ala Laribi, Sahar Aouf, Sallouha Gabbouj, Noureddine Bouaouinaa, Abdelfattah Zakhama & Hedi Harizi

  2. Department of Cancerology and Radiotherapy, Farhat Hached University Hospital, Monastir, Tunisia

    Noureddine Bouaouinaa

  3. Department of Anatomy and Pathologic Cytology, Fattouma Bourguiba University Hospital, Monastir, Tunisia

    Abdelfattah Zakhama

  4. Faculty of Dental Medicine, University of Monastir, of Monastir, 5019, Monastir, Tunisia

    Hedi Harizi

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  1. Ala Laribi
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Correspondence to Hedi Harizi.

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Laribi, A., Aouf, S., Gabbouj, S. et al. Human glutathione peroxidase codon 198 variant increases nasopharyngeal carcinoma risk and progression. Eur Arch Otorhinolaryngol 278, 4027–4034 (2021). https://doi.org/10.1007/s00405-021-06628-5

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