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Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis

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Abstract

Background

Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GST-T1, p53 polymorphisms on brain tumor was investigated.

Methods and results

Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient’s demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (χ2 = 39.756, p < 0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (χ2 = 0.335, p = 0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (χ²=2.536, p = 0.281).

Conclusion

The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.

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Data Availability

The authors confirm that all data supporting the finding of the study are available within the article, and the raw data supporting the findings were generated and available at the corresponding author on request.

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Acknowledgements

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Funding

The authors declared that this study has received no financial support.

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Contributions

Authors’ contributions: OD, SO: Conceptualization, Methodology, Formal analysis. OD, PK, AAH, SYS, CY, YI: Data management. NÜ: Graphical design. AAH, OD: Writing, Reviewing and Editing. All authors have read and approved the manuscript.

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Correspondence to Onur Dirican.

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The authors declare no competing interests.

Ethics approval and consent to participate

Ethics committee approval was received for this study from the IRB Health Sciences University Keçiören Education and Research Hospital (No: 2012-KAEK-15/1810, date:27.02.2019). The participant received detailed explanations about the study, and written informed consents were obtained. The study was designed and conducted according to relevant ethical regulations and was performed with respect to the Declaration of Helsinki and its later amendments.

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Dirican, O., Kaygın, P., Oğuztüzün, S. et al. Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis. Mol Biol Rep 51, 45 (2024). https://doi.org/10.1007/s11033-023-08985-2

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