Page 123 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

SDIRSACR Oncology Insights

SESSION 6

CANCER EPIDEMIOLOGY- STRATEGIES FOR PREVENTION AND EARLY DETECTION

P26

Glutathione-S transferase omega 1 and omega 2 gene polymorphisms modify susceptibility to brain
tumor development

Đurđa Jerotić 1,2,3 , Marko Todorović4, Tamara Stanisavljević 1,2,3 , Mihailo Milićević , Vuk Šćepanović , Aleksandar
1,4
1,4
Stanimirović , Marija Plješa-Ercegovac 1,2,3 , Ana Savić-Radojević 1,2,3
1,4
1Faculty of Medicine, University of Belgrade, Belgrade, Serbia
2Institute of Medical and Clinical Biochemistry, Belgrade, Serbia
3Center for Excellence for Redox Medicine, Belgrade, Serbia
4Clinic of Neurosurgery, University Clinical Centre of Serbia, Belgrade, Serbia

Keywords: brain tumor, glutathione S-transferase omega, gene polymorphism

Background: Glutathione S-transferases (GSTs) play critical roles in detoxification, redox homeostasis, and modulation
of cellular signaling pathways, thus participating in tumorigenesis through effects on cell survival, proliferation, and drug
resistance. Among them, the omega-class of GSTs (GSTO1 and GSTO2) exhibit distinct enzymatic functions, including
thioltransferase and dehydroascorbate reductase activity, contributing to the regulation of redox homeostasis and
protein function. Given the central role of reactive oxygen species in brain tumor pathogenesis, and the fact that GSTO
genes are highly polymorphic, investigating their variants may provide insight into individual susceptibility to brain
tumor development.
Material and methods: GSTO1 rs4925 and GSTO2 rs156697 gene polymorphisms were determined by the qPCR
method in 111 patients with brain tumors (classified into gliomas, meningiomas and other tumor types including
pituitary adenomas and less common intracranial neoplasms) and 140 age- and gender- matched healthy controls.
Results: Homozygous carriers of the GSTO1 variant *A allele had a significantly reduced overall risk of brain tumor
development compared to carriers of the referent genotype (OR=0.26, 95%CI:0.08-0.86, p=0.027). Subgroup analysis
revealed that the observed significance was driven by the association between GSTO1 polymorphism and the risk of
developing pituitary adenomas and less common intracranial neoplasms (OR=0.25, 95%CI:0.09-0.67, p=0.013), while
no statistically significant associations were found for gliomas or meningiomas. The additional haplotype analysis
confirmed that individuals with the GSTO H2 haplotype, defined as the concomitant presence of the variant GSTO1*A
and GSTO2*G alleles, had decreased risk of developing pituitary adenomas and less common intracranial neoplasms
(OR=0.13, 95%CI:0.02-0.74, p=0.023). Conversely, individuals with H3 haplotype including referent GSTO1*C and variant
GSTO2*G alleles were at significantly higher risk for glioma (OR=2.94, 95%CI:1.21-7.15, p=0.018) and meningioma
(OR=4.08, 95%CI:1.19-13.94, p=0.026).
Conclusion: Our results suggest that GSTO locus variants may influence susceptibility to brain tumors depending on
the histological subtype. These findings support further investigation into GSTO variants as potential genetic markers
for brain tumor risk stratification.

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