• Katerina Trenceva Institute of Public Health of the Republic of North Macedonia, Skopje, Republic of North Macedonia
  • Aleksandar Eftimov Institute of Pathology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Aleksandar Petlichkovski Institute of Immunobiology and Human Genetics, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Dushko Lukarski University Clinic of Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Ilir Ismail University Clinic of Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Meri Peshevska University Clinic of Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Nikola Vasev University Clinic of Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Sonja Topuzovska Institute of Medical and Experimental Biochemistry, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia


radiotherapy, confounding factors, breast cancer, FDXR, CCNG1, gene expression


Introduction: CCNG1 and FDXR are well-established gene expression biomarkers of IR exposure. Expression alterations during radiotherapy (RT) in patients with different types of cancer has seldom been investigated, along with their potential associations with biochemical- and lifestyle-related confounding factors, that would help elucidate specific changes in RT response and individualize RT in breast cancer patients.

Materials and methods: A non-randomized, controlled, open-trial clinical study was performed in 57 breast cancer patients (intervention group, IG) and 56 healthy individuals (control group, CG). Gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in leukocytes of peripheral blood samples.

Results: A significant up-regulation of FDXR was observed up to 48 h after the first RT fraction, with no significant expression alterations of CCNG1 at 24 h and 48 h. Fold changes of CCNG1 were slightly lower (1.13-1.23) compared to FDXR (1.49-2.08). RT-induced FDXR and CCNG1 expression alterations could not be significantly associated with patient age, increased WBC count (> 9x109/L), increased C-reactive protein (CRP) during RT (> 5 mg/L) and decrease of increased CRP values during RT. Patients with diabetes mellitus had lower CCNG1 fold changes 24 h post-RT (0.89 ± 0.3 vs. 1.23 ± 0.6); identical was the finding for smokers and non-smokers (1.06 ± 0.5 vs. 1.22 ± 0.7).

Conclusion: RT-induced CCNG1 and FDXR changes could not be significantly associated with the examined biochemical- and lifestyle confounding factors, except for diabetes mellitus and smoking.


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