MF OI Onkologijos mokslo laboratorija (04.05.02)

Laryngeal cancer is a relatively uncommon malignancy with predisposing genetic factors that remain unclear. Single-nucleotide polymorphisms (SNPs) in genes involved in innate immune signaling may contribute to the development and progression of laryngeal carcinoma. This study aimed to evaluate the association of TLR4 (rs7037225, rs11536889, rs7037117) and MYD88 (rs7744, rs6853) polymorphisms with the risk of laryngeal squamous cell carcinoma (LSCC), as well as its clinical and pathological characteristics and survival. A retrospective case–control study involving 172 LSCC patients and 220 healthy controls was conducted. Genotyping was performed using real-time PCR from venous blood samples. MYD88 rs7744 was significantly associated with tumor size and lymph node involvement. Survival analysis showed a significant association between rs7744 and recurrence-free survival (RFS), with the AG and GG genotypes linked to poorer outcomes. Conversely, carriers of the TLR4 rs7037225 CT genotype showed significantly improved RFS, with p ranging from 0.024 to 0.037 across models. Considering the significant roles of TLR4 and MYD88 in Toll-like receptor signaling, these findings may reflect the involvement of innate immune pathways in LSCC progression. In summary, MYD88 rs7744 was associated with clinicopathological features and RFS, while TLR4 rs7037225 appeared to have a potential protective effect on survival.

Atopic dermatitis (AD) is a chronic inflammatory skin disease increasingly prevalent in adults. Vitamin D plays an important role in regulating immune responses, cellular differentiation, and inflammation. Several single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been suggested as biomarkers of AD susceptibility and severity. The aim of this study was to investigate six SNPs in the VDR gene (rs3847987, rs731236, rs7975232, rs1544410, rs2228570, and rs11168293) and their association with AD and blood biomarkers. Genotyping was performed in 91 adult patients with AD and 102 controls using real-time polymerase chain reaction. The genotype and allele distributions did not differ significantly between AD patients and controls. However, the G and T alleles of VDR rs731236 and rs1544410 were more frequently detected in individuals with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/mL. In contrast, the VDR rs7975232 C allele appears to be associated with lower odds of having a serum 25(OH)D level above 30 ng/mL. In genotype-stratified analysis, the T allele of VDR rs11168293 was more prevalent among individuals with eosinophil counts of 300 cells/μL. These findings suggest that VDR polymorphisms may contribute to variability in vitamin D status and inflammatory responses in adults with AD.

Background and Objectives Breast cancer remains the most commonly diagnosed cancer among women globally. The complicated tumor microenvironment, aggressive behavior, heterogeneous nature, elevated proliferation rate, and treatment resistance are among the most characterized hallmarks of breast cancer. Many of these processes relate to the capacity of cancer cells to avoid apoptosis. Overexpressing anti-apoptotic genes is one strategy by which cancer cells prevent apoptosis. Consequently, anti-apoptotic gene expression reduction can promote the apoptosis mechanism and enhance the cells' sensitivity to cancer therapy. Chemical therapies are effective in treating cancer, but their adverse effects and resistance frequently result in treatment failure. Consequently, plant-based substances have recently received a lot of attention for their ability to inhibit cancer cell survival and increase sensitivity to treatment. One of these phytochemicals is sulforaphane (SFN), which can be found in cruciferous vegetables like broccoli and cauliflower. SFN possesses various attributes, including anti-inflammatory, cardioprotective, antioxidative, cytoprotective, and antimicrobial properties; however, its anticancer property is the most significant. Several studies demonstrated that SFN might induce apoptosis and inhibit the expression of cancer-specific genes. Thus, this study aimed to investigate the in vitro effects of SFN on breast cancer cells by evaluating BCL2 and BCL2L1 expression at both the gene and protein levels. Material and Method In this study, MCF-7 and MDA-MB-231 breast cancer cell lines were used. Cells were seeded in plates and incubated overnight. The next day, cells were treated with 25 µM and 50 µM concentrations of SFN or with DMSO as a control (0 µM). After 48 hours of incubation time, the expression of BCL2 and BCL2L1 genes was determined using reverse transcription-quantitative PCR (RT-qPCR). The total RNA was extracted from cells using the RNeasy Mini Kit. One microgram of total RNA was converted into cDNA using the High-Capacity RNA-to-cDNA Kit. RT-qPCR analysis was performed on a QuantStudio3 Real-Time PCR System. Relative gene expression was normalized to β-actin. BCL-2 and BCL-XL protein levels were assessed using Western blot analysis, involving separation by gel electrophoresis and transfer onto a membrane utilizing the semi-wet transfer unit Mini Blot module. Target proteins were detected using specific primary and secondary antibodies. The visualization of chemiluminescent imaging was done utilizing the Azure 280 system. The target protein expression level was normalized using the GAPDH protein as an internal control. Statistical analysis was performed using IBM SPSS Statistics 30 (version 30.0.0.0), and statistical significance was defined as a p-value less than 0.05. Results In MCF-7 cells, after the treatment with 25 µM and 50 µM concentrations of SFN, the BCL2 gene expression was reduced to 0.44 and 0.33, and BCL2L1 gene expression was 0.83 and 0.73, respectively. Additionally, BCL-2 protein levels decreased to 0.56 and 0.33 after the same SFN concentrations. The level of the BCL-XL protein did not alter significantly. In MDA-MB-231 cells, the BCL2 gene expression reduced to 0.88 and 0.82, and BCL2L1 gene expression was 0.73 and 0.32 after the treatment with 25 µM and 50 µM concentrations of SFN, respectively. Also, the concentrations of SFN used statistically significantly reduced protein levels. BCL-2 protein levels decreased to 0.85 and 0.78, and BCL-XL was 0.84 and 0.63. Conclusions and Recommendations Our study results revealed that SFN reduce the gene expression and protein levels of BCL2 and BCL2L1 in breast cancer cells. This suggests that SFN may be a potential anticancer agent whose effects are associated with the regulation of BCL-2 family proteins in the treatment of breast cancer.

Background and Objectives Breast cancer (BC) is a biologically heterogeneous disease with diverse molecular subtypes and clinical outcomes, strongly influenced by genetic factors. ATP-binding cassette (ABC) transporters play an important role in transmembrane processes, including drug efflux, cellular detoxification, and the maintenance of intracellular homeostasis. Variants in genes such as ABCB1 and ABCB8 may contribute to interindividual differences in tumor behavior, influencing clinicopathological characteristics and potentially affecting disease progression and treatment response. This study evaluated the association of two single nucleotide polymorphisms (SNPs), ABCB1 rs1128503 and ABCB8 rs56198402, with BC clinicopathological features. The findings aim to clarify their role in tumor biology and assess their potential as prognostic biomarkers, contributing to a better understanding of the genetic background of BC heterogeneity. Material and Method The study population comprised 170 female patients with histopathologically confirmed early-stage primary BC, aged 30 to 74 years (median age: 46 years). Clinical and tumor pathomorphological data, including tumor size, lymph node involvement, presence of metastases, degree of differentiation, estrogen (ER) and progesterone (PR) receptor status, human epidermal growth factor receptor 2 (HER2) status, disease progression, and mortality, were obtained from oncologists and the follow-up period extended until November 30, 2024. Genomic DNA was extracted from peripheral blood leukocytes using a column-based commercial DNA isolation kit in accordance with the manufacturer’s instructions. Genotyping of ABCB1 rs1128503 and ABCB8 rs56198402 was performed using TaqMan probe-based assays on the QuantStudio™ 3 Real-Time PCR System. The strength of associations between SNPs and BC clinicopathological characteristics was estimated using crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Survival outcomes were assessed using Kaplan-Meier analysis. Statistical analysis was conducted using IBM SPSS Statistics, version 30.0.0.0, and a p-value < 0.05 was considered statistically significant. The study protocol was approved by the Kaunas Regional Biomedical Research Ethics Committee (approval numbers BE-2-10 and P1-BE-2-10/2014). Results Significant associations were identified between ABCB1 rs1128503 and PR status, metastatic disease, disease progression, and mortality. Specifically, GA genotype carriers had higher odds of progesterone receptor positivity than GG (OR=2.038; 95% CI 1.016–4.091; p=0.045), which was corroborated by allele-based analysis, showing similarly increased odds among A allele carriers (OR=1.986; 95% CI 1.034–3.816; p=0.039). Conversely, GA carriers demonstrated reduced odds of metastasis (OR=0.301; 95% CI 0.122–0.742; p=0.009), disease progression (OR=0.387; 95% CI 0.171–0.877; p=0.023), and mortality (OR=0.361; 95% CI 0.144–0.907; p=0.030). Furthermore, tumor size and lymph node involvement were also significantly associated (p-value < 0.05) with the studied genotype, indicating a protective effect against more advanced disease features. A significant difference in progression-free survival was observed across ABCB1 rs1128503 genotypes, with the GA genotype associated with more favorable outcomes (p-value < 0.05). No significant associations were found between the ABCB8 rs56198402 and clinicopathological characteristics of BC. Conclusions and Recommendations The ABCB1 rs1128503 was significantly associated with several breast cancer clinicopathological features, including progesterone receptor status, metastasis, disease progression, and progression-free survival, suggesting a potential protective effect of the GA genotype. In contrast, no significant associations were found for the ABCB8 rs56198402 variant. Further studies with larger cohorts are needed to confirm these findings and clarify the biological role of ABCB1 variants in breast cancer progression and prognosis.

Background and Objectives Breast cancer (BC) is a heterogenous disease characterized by substantial variability in tumor biology and clinical behavior. This heterogeneity is reflected in clinicopathological features, including hormone receptor status, human epidermal growth factor receptor 2 (HER2) expression, tumor histological grade, tumor size, and disease stage, which describe tumor features and are key determinants of prognosis. Single nucleotide polymorphisms (SNPs) have been proposed as potential contributors to inter-individual differences in these tumor features and clinical outcomes; however, their role in early-stage BC remains insufficiently defined. In this study, polymorphisms in the RRP1B gene, specifically rs2838342 and rs2051407, were investigated for their potential associations with BC features and outcomes. Material and Method Study population. A total of 191 adult female patients with primary stage I-II BC were enrolled. All participants provided written informed consent, and the study was approved by the Kaunas Regional Ethics Committee for Biomedical Research (nos. BE-2-10 and P1-BE-2-10/2014). Peripheral blood samples were collected for genetic analysis. DNA extraction and genotyping. Genomic DNA was extracted from peripheral blood using a spin column-based extraction method with a commercially available kit. SNP genotyping was performed using TaqMan allelic discrimination assays on a Quanstudio 3 Real-Time PCR System. Statistical analysis. Associations between SNPs and clinicopathological features as well as binary clinical outcomes (disease progression, metastasis status, and mortality status) were evaluated using logistic regression under an additive genetic model. Both univariate and age-adjusted multivariable analyses were performed. Sensitivity analyses using alternative genetic models were conducted for selected SNPoutcome associations showing non-linear patterns in genotype distributions. Progression-free, overall, and metastasis-free survival (MFS) were analyzed using Kaplan-Meier with log-rank tests and Cox proportional hazards regression models under an additive genetic model. Multivariable Cox models were adjusted for established clinicopathological prognostic factors. To account for multiple testing, the Benjamini-Hochberg false discovery rate (FDR) correction was applied separately for clinicopathological features (n = 12), binary clinical outcomes (n = 6), and Cox models (n = 6), using p-values from fully adjusted additive models. Kaplan-Meier analyses were considered descriptive and were not included in correction. Adjusted p-values (q-values) < 0.05 were considered significant. All statistical analyses were performed using IBM SPSS Statistics 30.0.0.0. Results Genotype distributions were as follows: for rs2838342, AA 30.9% (n = 59), AG 51.8%, (n = 99), and GG 17.3% (n = 33); for rs2051407, CC 36.6% (n = 70), CT 45.5 % (n = 87), and TT 17.8% (n = 34). The minor allele frequencies were 43.2% for rs2838342 and 40.6% for rs2051407. Genotype frequencies for both SNPs were consistent with Hardy-Weinberg equilibrium (p > 0.05). In age-adjusted additive logistic regression models, rs2838342 was associated with tumor size (p = 0.022) and histological grade (p = 0.032), although neither association remained significant after correction for multiple testing. Under a recessive genetic model, rs2838342 was associated with estrogen receptor (ER) status after adjustment for age group (OR = 0.38, 95% CI 0.17-0.85, p = 0.018), suggesting a lower likelihood of ER positivity among GG homozygotes. A similar nonsignificant trend under the same genetic model was observed for rs2051407 (p = 0.072). Kaplan-Meier analyses showed no statistically significant differences in survival outcomes across genotype groups. Consistently, no associations were observed in Cox regression analyses under unadjusted or multivariable-adjusted models accounting for age and clinicopathological variables. All results remained non-significant after Benjamini-Hochberg FDR correction. Conclusions and Recommendations No statistically significant associations were observed between the studied SNPs and clinicopathological or survival outcomes after multiple testing correction. However, nominal and model-specific associations for rs2838342 indicate a potential role in tumor biology requiring validation in larger, independent cohorts.

Background and Objectives Germline pathogenic or likely pathogenic (P/LP) variants account for 5–10% of all breast cancer (BC) cases, with a higher prevalence of 10–20% observed in specific BC molecular subtypes, such as triple-negative breast cancer (TNBC). P/LP variants in established BC susceptibility genes are associated with an increased risk of BC and may contribute to distinct tumor phenotypes and clinical outcomes. This study aimed to evaluate the distribution of germline P/LP variants and their associations with clinicopathological features and clinical outcomes in BC patients. Material and Method A total of 85 female patients with stage I-II BC, including hormone receptor-positive (HR+)/HER2-negative (HER2−) (n=60) and TNBC (n=25), were included. Inclusion criteria required complete clinicopathological data (age at diagnosis, tumor size, tumor histological grade, lymph node involvement, and clinical outcomes) and absence of clinically significant comorbidities. Exome sequencing of germline DNA from peripheral blood was performed to identify variants in 13 BC susceptibility genes (BRCA1, BRCA2, CDH1, PTEN, STK11, TP53, ATM, CHEK2, PALB2, RAD51C, RAD51D, BARD1, and NF1). Variant analysis was conducted using the Franklin platform (Qiagen), and pathogenicity was re-evaluated according to current ENIGMA, ClinGen, and CanVIG guidelines. For statistical analysis, patients were stratified into P/LP variant carriers and non-carriers. Associations with clinicopathological features and clinical outcomes were assessed, with age included as a continuous covariate for adjustment. The study was approved by the Kaunas Regional Biomedical Research Ethical Committee (Nos. BE-2-10 and P1-BE-2-10/2014). Results Overall, 11 distinct P/LP variants were identified (six in BRCA1, three in CHEK2, and one each in BRCA2 and ATM). These variants were detected in 20/85 patients (23.5%), including 10/60 (16.7%) with HR+/HER2− BC and 10/25 (40%) with TNBC. Only one HR+/HER2− BC patient carried two variants; all others had a single variant. P/LP variants were significantly associated with BC molecular subtype (p=0.021), with carriers more likely to have TNBC (OR=3.33, 95% CI 1.17−9.52, p=0.025), although this was not significant after age adjustment (p=0.158). Carrier status was also associated with tumor grade (p=0.039), disease progression (p=0.007), and distant metastasis (p=0.035), but only the association for increased risk of disease progression for patients carrying P/LP variants remained significant after age adjustment (OR=3.09, 95% CI 1.01–9.43, p=0.048). In the TNBC subgroup, P/LP variant carrier status was statistically associated with lymph node involvement (p=0.009), with carriers having higher odds of lymph node involvement, even after age adjustment (OR=15.18, 95% CI 2.01–113.35, p=0.008), although this finding should be interpreted cautiously due to the small sample size. Survival analysis showed a significant association between P/LP variant carrier status and progression-free survival (PFS) in the overall cohort (p=0.011), which was likely driven by the HR+/HER2− BC subgroup (p=0.030) but not TNBC (p=0.154). In HR+/HER2− patients, carriers had a higher risk of shorter PFS in univariate analysis (HR=2.8, 95% CI 1.05–7.54, p=0.039), which was not significant after age adjustment (p=0.084). For metastasis-free survival (MFS), a significant difference was observed in the overall cohort (p = 0.039), but not in subtype-specific analyses. Although carriers showed a higher risk of shorter MFS in univariate analysis (HR=2.41, 95% CI 1.02– 5.72, p=0.046), this did not remain significant after adjustment for age (p=0.073). Conclusions and Recommendations Germline P/LP variants were identified in a substantial proportion of BC patients, with a higher prevalence in TNBC. Although carrier status was associated with more aggressive disease features, particularly disease progression, most associations did not remain significant after adjustment for age. These findings suggest that P/LP variants may contribute to BC heterogeneity, although their independent prognostic value appears limited and requires further investigation in larger cohorts.

Background and Objectives Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare but aggressive head and neck malignancy, characterized by poor prognosis and low survival rates. Despite advances in treatment, the molecular mechanisms underlying HSCC development and progression remain misunderstood. The MYD88 gene, which encodes a crucial adaptor protein in innate immune signaling pathways, and its dysregulation have been linked to oncogenesis across many tumor types. However, the role of MYD88 genetic variants in HSCC has not been thoroughly investigated. Material and Method This retrospective case–control study was conducted in the Lithuanian University of Health Sciences, Department of Otorhinolaryngology, between 2017 and 2024, including 79 male patients with histologically confirmed HSCC and 220 healthy male controls. Clinical and pathological data were collected from medical records. Genomic DNA was extracted from peripheral blood samples, and selected MYD88 polymorphisms (rs7744 and rs6853) were genotyped using real-time PCR with TaqMan probes in the Oncology Research Laboratory, Institute of Oncology. Statistical analyses were performed using SPSS (version 30.0). Results The MYD88 rs7744 polymorphism was significantly associated with distant metastasis. Carriers of the GG genotype had a markedly increased risk compared to AA genotype carriers (OR = 28.46, 95% CI: 1.85–438.82, p = 0.016). No significant associations were observed between MYD88 polymorphisms and HSCC susceptibility, relapse-free survival, or overall survival. Additionally, rs6853 showed no association with clinicopathological features. Conclusions and Recommendations The MYD88 rs7744 variant might play a role in tumor progression, specifically regarding distant metastasis, rather than in susceptibility to HSCC.

Background and Objectives Breast cancer is a leading cause of cancer-related deaths globally. According to WHO data, in 2022, BC accounted for 6.8% of cancer-related deaths worldwide and 6.2% of such deaths within the Lithuanian population. One of the mechanisms underlying BC is the influence of genetic variants. High-frequency, low-penetrance genetic variants, including single nucleotide polymorphisms (SNPs), are more frequently linked to sporadic breast cancer. The epithelial-to-mesenchymal transition (EMT) is a cellular process that plays a role in embryonic development, wound healing, and tumor formation. EMT is crucial in invasion and subsequent metastasis. Snail1, encoded by the SNAI1 gene, is one of the key factors triggering EMT. In this study, we focused on SNAI1 rs8120550, rs1543442, and rs73113648 polymorphisms and their impact on various pathomorphological features and patients’ prognosis within the Lithuanian breast cancer cohort. Material and Method A total of 199 breast cancer patients were studied. The inclusion criteria were as follows: confirmed diagnosis, early BC stage (I–II), and complete medical documentation. Clinicopathological information was collected from medical records in collaboration with oncologists. Polymorphisms of interest were analyzed with real-time PCR-based genotyping. Statistical analysis was performed using SPSS (31.0.0.0). A pvalue < 0.05 was considered statistically significant. The study received approval from the Kaunas Regional Biomedical Research Ethical Committee (no. BE-2-10, no. P1- BE-2-10/2014,), and written informed consent was obtained from all participants. Results Pearson’s chi‑square analysis revealed significant associations between SNAI1 rs8120550 and disease progression (p = 0.011) and metastasis (p = 0.008). Additionally, rs73113648 was significantly associated with age group (p = 0.041), disease progression (p = 0.002), and metastasis (p = 0.002). In univariate logistic regression analysis, for SNAI1 rs73113648, the TT genotype was significantly associated with older age at diagnosis, showing lower odds compared with the CC genotype (OR = 0.247, p = 0.036). In the analysis of clinical outcomes for rs73113648, the TT genotype was statistically associated with higher odds of progression and metastasis compared with CC genotype (OR = 6.207, p = 0.001; OR = 5.952, p = 0.002, respectively). Rs8120550 demonstrated significant associations with disease progression and metastasis, where the AG genotype was associated with significantly higher odds than the AA genotype (OR = 2.718, p = 0.005; OR = 2.872, p = 0.005, respectively). The following are results after Kaplan-Meier method, which was used to evaluate the association between SNPs and PFS, MFS and OS: rs8120550 showed significant results for PFS (p = 0.012) and for MFS (p = 0.009), while rs73113648 demonstrated statistically significant associations with PFS (p = 0.001) and MFS (p = 0.004). Rs1543442 demonstrated no significant associations with any survival outcomes. In univariate Cox regression analysis, rs8120550 (AG versus AA) were associated with shorter PFS (HR = 2.323, p = 0.006) and MFS (HR = 2.529, p = 0.006), while rs73113648 (TT versus CC) was linked to even shorter PFS (HR = 3.650, p < 0.001) and MFS (HR = 3.567, p = 0.002). Conclusions and Recommendations The study revealed that SNAI1 rs8120550 and rs73113648 were significantly associated with an increased risk of disease progression and metastasis. Both SNPs were also associated with poorer PFS and MFS, with rs73113648 showing the strongest effect. These findings suggest that SNAI1 polymorphisms may have prognostic value for clinical outcomes in early-stage BC, but further studies involving a larger, independent cohort, are recommended to confirm our findings.

Background and objectives Cervical cancer remains one of the major public health challenges, holding the position as the fourth-most prevalent cancer affecting women worldwide. Persistent infection with human papillomavirus (HPV) is a necessary prerequisite for cervical carcinogenesis; however, it is increasingly recognized that additional cofactors contribute to disease initiation and progression, including genetic susceptibility, premature sexuality, high parity, and tobacco use. Growing attention is being directed toward the role of genetic variation in modulating individual susceptibility and influencing disease progression. In this context, CDKN2A and CDKN2C encode key regulators of cell cycle control that influence cell proliferation and may be implicated in carcinogenic pathways. Investigating single-nucleotide polymorphisms (SNPs) in these genes may enhance understanding of the molecular mechanisms underlying cervical cancer, enable the identification of higher-risk individuals, and support the development of more personalized preventive and therapeutic strategies. The present study aimed to evaluate the impact of CDKN2A rs3088440 and CDKN2C rs12855 on the clinicopathological characteristics of cervical cancer, as well as on patients' overall and progression-free survival outcomes. Material and Method In this study, CDKN2A rs3088440 and CDKN2C rs12855 were screened in 165 women with stage I-IV cervical cancer. Clinicopathological data, including age at diagnosis, tumor size, lymph nodes involvement, tumor histological grade, disease progression, distant metastasis status, and mortality status, were collected by oncologists. Genomic DNA was isolated from peripheral blood samples using a spin column-based extraction method. Genotyping of SNPs was performed using TaqMan probe assays on the QuantStudio™ 3 Real-Time PCR System. Associations between SNPs and clinicopathological characteristics of cervical cancer were evaluated using odds ratios (ORs) with 95% confidence intervals (CIs). Associations with survival outcomes were assessed using Kaplan-Meier (with the log-rank test) and Cox regression analyses, reporting hazard ratios (HR) and 95% CIs. Progression-free survival (PFS) was defined from diagnosis to local or distant disease progression, while overall survival (OS) was assessed from diagnosis to death or last follow-up. All statistical tests were conducted using IBM SPSS Statistics 30.0.0.0, and p<0.05 was considered statistically significant. The study was approved by the Kaunas Regional Biomedical Research Ethical Committee (numbers BE-2-10 and P1-BE-2-10/2014). Results In the cohort of 165 patients, the genotype distribution of CDKN2A rs3088440 was 85.5% GG, 13.3% GA, and 1.2% AA, with corresponding allele frequencies of 92.1% (G) and 7.9% (A). For CDKN2C rs12855, genotype frequencies were 92.7% CC and 7.3% CT, while allele frequencies were 96.4% (C) and 3.6% (T). No significant associations were observed between these genotypes or alleles and the clinicopathological characteristics of cervical cancer. However, survival analysis using Kaplan-Meier curves revealed a significant difference in OS according to CDKN2A rs3088440 (p=0.009) and CDKN2C rs12855 (p=0.020) genotypes. The CDKN2A rs3088440 AA genotype was associated with poorer OS, while the CDKN2C rs12855 CT genotype was linked to more favorable OS. These findings were further supported by Cox regression analysis, indicating an increased risk of death associated with CDKN2A rs3088440 AA genotype and a reduced risk associated with CDKN2C rs12855 CT (HR=6.564; 95% CI 1.566-27.519; p=0.010, and HR=0.134; 95% CI 0.018-0.979; p=0.048, respectively). Additionally, a significant association was observed between CDKN2A rs3088440 genotypes and PFS (p=0.034). It was estimated that the CDKN2A rs3088440 AA genotype was associated with worse PFS (HR=5.198; 95% CI 1.245-21.701; p=0.024). Conclusions and Recommendations The findings suggest that CDKN2A rs3088440 and CDKN2C rs12855 polymorphisms were associated with OS and PFS, highlighting their potential as prognostic biomarkers in cervical cancer; however, larger studies are required to confirm these associations and their clinical utility.

Objectives: The aim of this study was to assess the impact of polymorphisms in cytokine genes on pain severity and pain treatment with palliative radiotherapy.