Page 132 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

Serbian Association for Cancer Research SDIRSACR

Acknowledgments and funding: This research was supported by the Serbian Academy of Sciences and Arts and the
IMGGE Annual Research Program for 2025, the Ministry of Science, Technological Development and Innovation of the
Republic of Serbia, 451-03-136/2025-03/200042.

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GPX1 gene polymorphism (rs1050450) affects overall survival of patients with prostate cancer: Serbian
cohort study

Milica Djurkic , Veljko Santric , Tanja Radic , Ana Savic-Radojevic , Djurdja Jerotic , Smiljana Mihailovic , Vladimir
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Vasic , Milos Petrovic , Uros Bumbasirevic , Tatjana Simic 4,5,8 , Marina Nikitovic , Vesna Coric 4,5
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1Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
2Clinic of Urology, University Clinical Center of Serbia, Belgrade, Serbia
3Institute of Mental Health, Belgrade, Serbia
4Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
5Center of Excellence for Redox Medicine, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
6The Obstetrics and Gynecology Clinic Narodni Front, Belgrade, Serbia
7Department of Urology, University Medical Center Zvezdara, Belgrade, Serbia
8Serbian Academy of Sciences and Arts, Belgrade, Serbia
Keywords: glutathione peroxidase 1, gene polymorphism, prostate cancer, survival
Background: It is well established that redox homeostasis plays an important role in both the development and
progression of cancer. Glutathione peroxidase 1 (GPX1) seems to be one of the main regulators of intracellular hydrogen
peroxide (H O ) levels. By altering its enzymatic activity, the GPX1 gene polymorphism might affect H O concentration,
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thus, alternating signaling pathways involved in apoptosis and cell proliferation. The aim of this study was to evaluate
the possible prognostic role of GPX1 rs1050450 gene polymorphism in patients with prostate cancer (PC).
Material and Methods: Total of 235 Serbian patients aged 68.84 ± 6.95 with pathohistologically confirmed prostate
cancer were included in this study. DNA was isolated from whole blood and GXP1 rs1050450 gene polymorphism was
determined by real-time polymerase chain reaction (PCR). To address the possible prognostic role of this polymorphism,
patients’ survival outcomes were followed from 2014-2022. For the analysis of the overall survival, Kaplan-Meier curves
were generated. Two distinctive models were composed to inspect not only the independent, but also the combined
effect of this gene polymorphism with known prognostic risk factors to evaluate the hazard ratio (HR) for the fatal
outcome.
Results: Most patients had prostate-specific antigen (PSA) over 20 ng/mL at the time of diagnosis and Gleason score 6.
During the follow-up period of eight years, 13 (5%) patients were lost. Patients with GPX1*ProPro genotype, indicating
those with higher enzymatic activity, lived significantly shorter than those carrying at least one GPX1*Leu allele,
indicating lower enzymatic activity (p = 0.031). When analyzed independently, GPX1*ProPro genotype conferred 1.6
times higher risk for fatal outcome (HR = 1.65; 95% CI = 1.04 – 2.60; p = 0.034). However, when Gleason score and PSA
were included into the analysis, this risk increased to ~2.5 times (HR = 2.40; 95% CI = 1.36 – 4.24; p = 0.003).
Conclusions: Carriers of GPX1*ProPro genotype that have developed PC live shorter than those with at least one
GPX1*Leu allele. Likewise, they have an increased risk of fatal outcomes, both independently and when combined
with other prognostic risk factors. These results suggest that GPX1 rs1050450 gene polymorphism might be used as a
prognostic biomarker in patients with prostate cancer.

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