Page 125 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

SDIRSACR Oncology Insights

Materials and Methods: We analyzed genotype data from the 1000 Genomes Project (EAS and EUR populations)
and a cohort of healthy Serbian volunteers from our previous study, focusing on the rs712829 SNP. Genotype and
allele frequencies were calculated for each population, stratified by gender. Fisher’s exact test or chi-squared test was
applied to assess gender-based differences in genotype and allele distributions. All analyses were performed using R
version 4.3.3 (R Core Team, 2024) with the following packages: dplyr, tidyr, ggplot2, ggpubr, readr, and stringr.
Results: In the EAS population, the G/G genotype predominated in both females (87.7%) and males (89.8%), with
low frequencies of G/T (11.9% and 9.8%, respectively) and T/T (≤0.41%). In contrast, the EUR population showed
more variability: in females, G/G occurred in 46.8%, G/T in 45.2%, and T/T in 8.0%; in males, G/G was 49.6%, G/T in
37.9%, and T/T in 12.5%. Allele G was more frequent in EAS (F: 93.6%, M: 94.7%) than in EUR (F: 69.4%, M: 68.5%).
Gender-based comparisons in both EAS and EUR populations showed highly significant differences in genotype and
allele distributions (Fisher’s exact and chi-square tests, all p-values < 0.01). In the cohort from SRB population (n=40),
genotype frequencies were G/G: 47.5%, G/T: 42.5%, and T/T: 10%. Allele G frequency was 68.8%, and allele T was
31.2%. No statistically significant differences by gender were observed in the Serbian population for either genotype (p
= 0.8) or allele frequencies (p=0.63).
Conclusions: Genotype and allele distributions of EGFR rs712829 significantly differ between East Asian and European
populations, with the EAS group exhibiting a much higher prevalence of the G allele. The Serbian population showed
a distribution more similar to EUR, with no significant gender-based differences. These findings underline population-
specific genetic variability and emphasize the importance of considering ethnicity and sex in pharmacogenetic and
epidemiological research involving EGFR variants.

Acknowledgments and funding: This work was supported by the Ministry of Science, Technological Development and
Innovation, Republic of Serbia, Agreements No. 451-03-136/2025-03/200378 and 451-03-137/2025-03/200111.

P29

The role of glutathione S-transferase omega 1 and omega 2 polymorphisms in susceptibility and
prognosis of colorectal cancer

Tamara Stanisavljevic 1,2,3 , Milica Stojkovic Lalosevic , Marija Pljesa Ercegovac 1,2,3 , Vesna Coric 1,2,3 ,Tatjana Simic 1,2,3,4 ,
1,5
Djurdja Jerotic 1,2,3 , Aleksandra Pavlovic , Marija Matic1,2,3
1,5
1Faculty of Medicine, University of Belgrade, Belgrade, Serbia
2Institute of Medical and Clinical Biochemistry, Belgrade, Serbia
3Center of Excellence for Redox Medicine, Belgrade, Serbia
4Serbian Academy of Sciences and Arts, Belgrade, Serbia
5Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, Belgrade, Serbia

Keywords: colorectal cancer; GSTO; polymorphism, risk, prognosis

Background: Despite advancements in screening programs, colorectal cancer (CRC) is still frequently diagnosed
at advanced stages. The glutathione S-transferase (GST) family of enzymes plays a key role in the detoxification of
xenobiotics. Among them, the omega class (GSTO) is particularly important for maintaining redox homeostasis,
regulating pro-inflammatory signaling, and modulating apoptosis and cell survival pathways. The aim of this study was
to evaluate the possible role of gene polymorphisms of the GSTO1 and GSTO2 in the risk and prognosis of CRC.
Materials and Methods: The study included 140 patients with a histopathologically confirmed diagnosis of CRC and 140
age and gender-matched controls. Genomic DNA was extracted from peripheral blood using the QIAamp DNA Blood
Mini Kit. GSTO1 (rs4925) and GSTO2 (rs156697) polymorphisms were determined using the real time PCR amplification
method. The median follow-up of patients was 44.00 (IQR 7.5) months.
Results: The obtained data showed thatcarriers of at least one GSTO1*A variant allele had a six-fold decreased CRC
risk compared to those carrying the referent GSTO1*CC genotype (OR=0.16, 95%CI=0.09–0.27, p<0.001). In the case of
the GSTO2 polymorphism, individuals with at least one variant GSTO2*G allele had a significantly decreased CRC risk
(OR=0.59, 95%CI=0.36–0.95, p=0.029) compared to individuals with the referent GSTO2*AA genotype. Additionally,
individuals carrying a combination of one variant allele of both GSTO1 and GSTO2 had a significantly lower CRC risk
(OR=0.30, 95%CI=0.18–0.50, p<0.001). These findings were confirmed by a haplotype analysis; the individuals with the
H3 haplotype, represented by one copy of the variant GSTO1 (*A) and one copy of the variant GSTO2 (*G) alleles had
the lowest CRC risk (OR=0.42, 95%CI=0.25-0.70, p=0.001). No statistically significant effect of either GSTO1 or GSTO2

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