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Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population

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Host genetic characteristics and environmental factors interactions may play a crucial role in cervical carcinogenesis. We investigated the impact of functional genetic variants of four xenobiotic-metabolizing genes (AhR, CYP1A1, GSTM1, and GSTT1) on cervical cancer development in Tunisian women.


The AhR gene polymorphism was analyzed using the tetra-primer ARMS-PCR, whereas the CYP1A1 polymorphism genotypes were identified by PCR-RFLP. A multiplex ligation-dependent polymerase chain reaction approach was applied for the analysis of GSTM1 and GSTT1 polymorphisms.


The homozygous A/A genotype of the AhR gene (rs2066853) and the heterozygous T/C genotype of the CYP1A1 SNP (CYP1A1-MspI) appeared to be associated with an increased risk of cervical tumorigenesis (ORa = 2.81; ORa = 5.52, respectively). Furthermore, a significantly increased risk of cervical cancer was associated with the GSTT1 null genotype (ORa = 2.65). However, the null GSTM1 genotype showed any significant association with the risk of cervical cancer compared to the wild genotype (ORa = 1.18; p = 0.784). Considering the combined effect, we noted a significantly higher association with cancer risk for individuals with at least two high-risk genotypes of CYP1A1/GSTT1 (ORa = 4.2), individuals with at least two high-risk genotypes of CYP1A1/GSTT1/AhR (ORa = 11.3) and individuals with at least two high-risk genotypes of CYP1A1/GSTM1/GSTT1/AhR exploitation low-risk genotype as a reference.


This study indicated that the single-gene contribution and the combined effect of xenobiotic-metabolizing gene polymorphisms (AhR, CYP1A1-MspI, GSTM1, and GSTT1) may have a considerable association with increased cervical cancer risk.

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Single Nucleotide Polymorphism.


Aryl hydrocarbon Receptor.


Cytochrome P450 1A1.


Glutathione S-transferase Mu 1.


Glutathione S-transferase Theta 1.


Transactivation Domain.


TATA-binding Protein.


World Health Organization.


International Federation of Gynecology and Obstetrics.


Squamous Intraepithelial lesion.


Low grade Squamous Intraepithelial lesion.


High grade Squamous Intraepithelial lesion.


Invasive Cervical Cancer.


Squamous Cell Carcinoma.


Cervical Adenocarcinoma.


Human Papillomavirus.


Polycyclic aromatic hydrocarbon.

Pap test:

Papanicolaou test.


Polymerase Chain Reaction.


Amplification Refractory Mutation System.


PCR-Restriction Fragment Length Polymorphism.


Statistical Package for the Social Sciences.

ORa :

Adjusted Odd Ratio.


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The authors thank all Tunisian subjects for their participation in this study. This work was supported by the Ministry of Higher Education and Scientific and Technological Research and the Ministry of Public Health of Tunisia. The authors thank Mr. Adel Rdissi and Dr. Manel Ben Taher for the English revision, and Pr. Asma Omezzine for her support in the statistical study.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Study design: A. H. and A. K., Patient enrollment and sample collection: A. H., N. B., and H. B., Experiments, data collection, and data analysis: A. H., N. B., S.S., F. D., M. D., Z. H., and A. K. Manuscript writing: A. H., S. S., M. D., and A. K., All authors revised the manuscript and approved its final version.

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Correspondence to Ahlem Helaoui.

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Helaoui, A., Sfar, S., Boudhiba, N. et al. Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population. Mol Biol Rep 50, 949–959 (2023).

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