Page 127 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

SDIRSACR Oncology Insights

are proteins involved in the repair of DNA damage. XRCC1 participates in base excision repair of DNA single-strand
breaks caused by ionizing radiation and alkylating agents, while Rad51 plays a crucial role in the repair of double-strand
breaks through homologous recombination. The aim of this study was to analyze the association of XRCC1 1196A>G
and RAD51 135G>C single nucleotide polymorphisms (SNPs) with the risk of rectal cancer occurrence in Serbia, as well
as their impact on the response to preoperative chemoradiotherapy.
Material and Methods: For XRCC1 SNP analysis, a total of 48 patients with locally advanced rectal cancer and 71
healthy controls were included in this case–control study. For RAD51 SNP analysis, 43 patients and 71 healthy controls
were analyzed. Restriction fragment length polymorphism analysis was used for genotyping. Statistical significance was
set at p < 0.05.
Results: The distribution of XRCC1 1196 A>G and RAD51 135G>C genotypes in patients and controls did not deviate from
Hardy–Weinberg equilibrium. Using both dominant and recessive models, the XRCC1 was not found to be associated
with an increased risk of rectal cancer. Examination of the association of polymorphisms in the XRCC1 Gln399Arg gene
with the response to therapy showed that the presence of the marker allele A carries a risk for a poor therapeutic
outcome (OR: 0.26, 95% CI: 0.07–0.99, p = 0.044). Analysis of RAD51 135G>C polymorphism showed no statistically
significant association with the risk of rectal cancer or response to chemoradiotherapy. However, in male patients, the
GG genotype showed an increased cancer risk (OR: 3.72, 95% CI: 1.34–10.36, p = 0.009).
Conclusions: Although a statistically significant association of RAD51 135G>C with disease risk in the male population
was demonstrated, a deviation from Hardy–Weinberg equilibrium was noted. This may be due to the small sample size,
thus these preliminary findings need to be validated using a larger case–control study. This study might be useful for
future meta-analyses and construction of multi-gene, population-specific cancer risk prediction panels.

Acknowledgments and funding: This work was funded by the STEPUPIORS Horizon Europe Project (European
Commission, Grant No. 101079217) and was supported by the Ministry of Science, Technological Development and
Innovation of the Republic of Serbia (Agreement No. 451-03-136/2025-03/ 200043).

P32

The clinical significance of ATG5, ATG10 and ATG16L1 genes polymorphisms in advanced melanoma

Bojana Cikota-Aleksić1, Milica Ćućuz2, Branko Dujović3, Jovana Pavlica3, Viktorija Dragojević-Simić1, Lidija Kandolf3

1Center of Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia
2Institute of Medical Research, Military Medical Academy, Belgrade, Serbia
3Clinic of Dermatovenerology, Military Medical Academy, Belgrade, Serbia

Keywords: Autophagy, Gene polymorphism, Melanoma, Survival

Background: Autophagy is a highly conserved catabolic process involved in maintaining cellular homeostasis. The role
of autophagy in tumors (including melanoma) is still controversial since it differs during malignant transformation/
progression. Of note, autophagy is often increased in BRAF-positive melanomas where it impairs the response to
targeted therapy. In this study, we analyzed six polymorphisms in autophagy-related genes (ATG16L1, ATG5 and ATG10)
regarding their impact on clinicopathological characteristics and melanoma course.
Patients and Methods: The total of 149 patients with advanced melanoma were genotyped for rs2241880, rs2245214,
rs510432, rs1864182, rs1864183 and rs1051423. Genotyping included DNA isolation from peripheral blood and allelic
discrimination using TaqMan genotyping SNP assays for the StepOne Plus Real Time PCR System.
Results: Frequencies of analyzed genotypes were similar to those reported for other European populations. No
association between ATG genotypes and clinical/pathologic characteristics was observed. However, ATG10 rs1864182
was associated with baseline (BL) absolute neutrophil count (ANC) (CC vs. AA; p=0.047), absolute platelet count (APC)
(C vs. AA; p=0.042), neutrophils-to-lymphocytes ratio (CC vs. A; p=0.026), monocytes-to-lymphocytes ratio (CC vs. A;
p=0.05), neutrophils x platelets x monocytes – to lymphocytes ratio (NPM/L) (CC vs. AA; p=0.016) and neutrophils x
platelets – to lymphocytes ratio (NP/L) (CC vs. AA; p=0.045), respectively. The ATG10 rs1864183 was associated with
BL ANC (CC vs. G; p=0.082), absolute monocyte count (CC vs. TT; p=0.04), APC (C vs. TT; p=0.014), NPM/L (CC vs. TT;
p=0.007) and NP/L (CC vs. TT; p=0.055), respectively. In addition, patients with at least one rs2245214 C allele had
better progression free survival (PFS) (p=0.029), distant metastasis free survival (DMFS) (p=0.012) and overall survival
(p=0.017), respectively. In BRAF-negative patients, the presence of rs1051423 T allele was associated with better PFS
(p=0.012), while patients with at least one rs1864182 allele had superior DMFS.

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