Search Results (377)

Cervical cancer remains a major health burden among women in sub-Saharan Africa, where screening is often limited. Persistent high-risk human papillomavirus (HR-HPV) infection is the principal cause, highlighting the need for accurate molecular diagnostics. This cross-sectional study evaluated the analytical performance of one mRNA assay, APTIMA^® HPV assay (APTIMA mRNA), and two DNA-based assays, the Abbott RealTime High Risk HPV assay (Abbott DNA) and Seegene Allplex™ II HPV28 assay (Seegene DNA), in 527 cervical samples from a South African tertiary hospital, focusing on 14 shared HR-HPV genotypes. Seegene DNA yielded the highest detection rate (53.7%), followed by Abbott DNA (48.2%) and APTIMA mRNA (45.2%). APTIMA mRNA showed a strong agreement with Abbott DNA (87.9%, κ = 0.80), 89.9% sensitivity, 91.2% NPV, and the highest accuracy (AUC = 0.8804 vs. 0.8681). The agreement between APTIMA mRNA and Seegene DNA was moderate (83.4%, κ = 0.70), reflecting target differences. Many DNA-positive/mRNA-negative cases likely represent transient infections, though some may be latent with reactivation potential, warranting a follow-up. In resource-constrained settings, prioritizing transcriptionally active infections through mRNA testing may enhance screening efficiency and reduce burden. Scalable, cost-effective assays with strong clinical utility are essential for broadening access and improving cervical cancer prevention. Further studies should assess the integration of mRNA testing into longitudinal screening algorithms. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Background/Objectives: Genetic polymorphisms in the BRCA2 gene have been implicated in breast cancer susceptibility. While numerous studies have investigated this polymorphism, its precise role in breast cancer development remains unclear. Furthermore, to the best of our knowledge, no related studies have been conducted in Azerbaijan. The aim of this study was to determine the distribution of the BRCA2 Met1915Thr polymorphism (rs4987117) in the Azerbaijani population and to evaluate its potential association with breast cancer risk. Methods: A total of 144 breast cancer patients and 152 healthy controls were recruited from the Oncology Clinic of Azerbaijan Medical University between 2021 and 2024. The Met1915Thr polymorphism was genotyped using PCR-RFLP and visualized on a 2% agarose gel. Results: A statistically significant association with increased breast cancer susceptibility was observed for the heterozygous Met/Thr genotype (OR = 1.83, 95%CI = 1.08–3.11, p = 0.02), the Thr allele (OR = 1.57, 95%CI = 1.12–2.20, p = 0.008), and under the dominant inheritance model (OR = 1.83, 95%CI = 1.15–2.90, p = 0.01). Notably, this association was more evident among individuals aged over 58 years, in whom the Met/Thr genotype conferred a significantly elevated risk (OR = 2.35, 95%CI = 1.17–4.73, p = 0.02). Conclusions: The BRCA2 Met1915Thr polymorphism is associated with an increased risk of breast cancer in the Azerbaijani population. These findings suggest a potential role of this polymorphism in breast cancer susceptibility and highlight the need for further studies in larger cohorts to validate these associations. Full article

Green tea, derived from the unoxidized leaves of Camellia sinensis (L.) Kuntze, is one of the least processed types of tea and is rich in antioxidants and polyphenols. Among these, catechins—particularly epigallocatechin gallate (EGCG)—play a key role in regulating cell signaling pathways associated with various chronic conditions, including cardiovascular diseases, neurodegenerative disorders, metabolic diseases, and cancer. This review presents a comprehensive analysis of recent clinical studies focused on the therapeutic benefits and potential risks of interventions involving green tea extracts or EGCG. A systematic literature survey identified 17 relevant studies, classified into five key areas related to catechin interventions: toxicity and detoxification, drug pharmacokinetics, cognitive functions, anti-inflammatory and antioxidant properties, and obesity and metabolism. Findings from these clinical studies suggest that the health benefits of green tea catechins outweigh the potential risks. The review highlights the importance of subject genotyping for enzymes involved in catechin metabolism to aid in interpreting liver injury biomarkers, the necessity of assessing drug–catechin interactions in clinical contexts, and the promising effects of topical EGCG in reducing inflammation. This analysis underscores the need for further research to refine therapeutic applications while ensuring the safe and effective use of green tea catechins. Full article

Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid malignancies. However, the extent of this oncogenic risk appears to vary between specific gene variants. Understanding the genotype–phenotype relationship is essential for patient counseling and management. This report presents a multigenerational family carrying the rare c.−118C > G variant in the 5′ untranslated region of ANKRD26, contributing to the discussion on variant-specific cancer predisposition. Case Presentation: Two sisters aged 57 and 60 presented with lifelong bleeding diathesis and moderate thrombocytopenia. Their symptoms included easy bruising, menorrhagia, and excessive postoperative bleeding. Genetic testing confirmed heterozygosity for the ANKRD26 c.−118C > G variant. Bone marrow analysis revealed abnormal megakaryopoiesis without evidence of dysplasia or somatic mutations. One sister underwent major surgery without complications when managed with prophylactic hemostatic therapy. Their family history included multiple female relatives with similar symptoms, although formal testing was limited. Notably, none of the affected individuals developed hematologic malignancy, and only one developed esophageal cancer, with no current evidence linking this variant to solid tumors. Conclusions: This case underscores the importance of distinguishing between ANKRD26 variants when assessing malignancy risk. While ANKRD26-RT is associated with myeloid neoplasms, the c.−118C > G variant may confer a lower oncogenic potential. Variant-specific risk stratification and genetic counseling are crucial for optimizing surveillance and avoiding unnecessary interventions in low-risk individuals. Full article

Persistent high-risk human papillomavirus (HR-HPV) infection is closely associated with the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. In recent years, the potential impact of viral co-infections on this process has also been investigated. This study investigated the presence of HR-HPV, HSV-1/2, and HHV-8 DNA in formalin-fixed paraffin-embedded (FFPE) cervical biopsy samples, as well as their association with lesion severity. A total of 276 FFPE cervical tissue samples were evaluated. Viral DNA was detected by real-time PCR. The samples were histopathologically classified as normal/non-dysplastic, low-grade (LSIL), and high-grade (HSIL) lesions. HR-HPV DNA was detected in 112 samples (40.6%), with the highest prevalence observed in the 30–39 age group (51.2%). Among the HPV-positive cases, 46.5% (52/112) had single-type infections, 32.1% (36/112) had multiple-type infections, and 21.4% (24/112) were untypable. Together, these categories accounted for all HPV-positive samples. The most common genotype was HPV-16 (16.7%). HHV-8 and HSV-2 DNA were not detected. HSV-1 DNA was detected in only three non-dysplastic, HPV-negative cervical samples. In conclusion, HR-HPV DNA was detected in 40.6% of cervical biopsy samples and showed a significant association with increasing histological severity, highlighting its critical role in the progression of cervical lesions. Although the absence of HHV-8 and HSV-2 suggests a limited contribution of these viruses to cervical disease, the use of a single real-time PCR assay limits the ability to draw generalized conclusions regarding their clinical relevance. Further large-scale, multicenter studies employing both tissue-based and serological approaches are needed to validate these findings and to better understand the dynamics of viral co-infections in cervical disease. Full article

Cervical cancer (CC) is the gynecological cancer with the highest incidence and mortality worldwide. High-risk oncogenic human papillomaviruses (HPV) genotypes 16 and 18 are the primary risk factors for developing this female neoplasm, with them being the etiological agents of 70% of cervical cancers. Despite the availability of various prevention strategies, laboratory tests capable of detecting the disease in its previous and early stages, and multiple treatment schemes, CC incidence and mortality rates remain high, due in part to the population’s rejection or disinterest in the current type of sampling. An alternative that could encourage women to take better care of their gynecological health is the availability of tests that detect biomarkers in non-cervical samples with high sensitivity and specificity. The detection of biomarkers in non-cervical samples (blood, serum, plasma, urine, and vaginal fluids) may help reduce the discomfort associated with cervical sampling in patients, therefore promoting gynecological healthcare. This review discusses current diagnostic methods and recent advances in CC biomarkers detected in non-cervical samples, emphasizing their potential for diagnosis, prognosis, and patient monitoring. We further discuss the challenges and future perspectives of applying these biomarkers in clinical practice. The results of this review show that there is a considerable range of biomarkers proposed as alternative tools with high efficacy. Their identification in previous stages of the disease and routinely in non-cervical samples could help reduce the incidence and mortality rates of CC. Full article

Intracranial tumors such as gliomas, meningiomas, and brain metastases induce complex alterations in brain function beyond their focal presence. Modern connectomic and neuroimaging approaches, including resting-state functional MRI (rs-fMRI) and diffusion MRI, have revealed that these tumors disrupt and reorganize large-scale brain networks in heterogeneous ways. In adult patients, diffuse gliomas infiltrate neural circuits, causing both local disconnections and widespread functional changes that often extend into structurally intact regions. Meningiomas and metastases, though typically well-circumscribed, can perturb networks via mass effect, edema, and diaschisis, sometimes provoking global “dysconnectivity” related to cognitive deficits. Therefore, this review synthesizes interdisciplinary evidence from neuroscience, oncology, and neuroimaging on how intracranial tumors disrupt functional brain connectivity pre- and post-surgery. We discuss how functional heterogeneity (i.e., differences in network involvement due to tumor type, location, and histo-molecular profile) manifests in connectomic analyses, from altered default mode and salience network activity to changes in structural–functional coupling. The clinical relevance of these network effects is examined, highlighting implications for pre-surgical planning, prognostication of neurocognitive outcomes, and post-operative recovery. Gliomas demonstrate remarkable functional plasticity, with network remodeling that may correlate with tumor genotype (e.g., IDH mutation), while meningioma-related edema and metastasis location modulate the extent of network disturbance. Finally, we explore future directions, including imaging-guided therapies and “network-aware” neurosurgical strategies that aim to preserve and restore brain connectivity. Understanding functional heterogeneity in brain tumors through a connectomic lens not only provides insights into the neuroscience of cancer but also informs more effective, personalized approaches to neuro-oncologic care. Full article

Stereotactic body radiotherapy (SBRT) delivers ablative radiation doses with sub-millimeter precision. Radiogenomic studies, meanwhile, provide insights into how tumor-intrinsic genetic factors influence responses to such high-dose treatments. This review explores the radiobiological mechanisms underpinning SBRT efficacy, emphasizing the roles of DNA damage response (DDR) pathways, tumor suppressor gene alterations, and inflammatory signaling in shaping tumor radiosensitivity or resistance. SBRT induces complex DNA double-strand breaks (DSBs) that robustly activate DDR signaling cascades, particularly via the ATM and ATR kinases. Tumors with proficient DNA repair capabilities often resist SBRT, whereas deficiencies in key repair genes can render them more susceptible to radiation-induced cytotoxicity. Mutations in tumor suppressor genes may impair p53-dependent apoptosis and disrupt cell cycle checkpoints, allowing malignant cells to evade radiation-induced cell death. Furthermore, SBRT provokes the release of pro-inflammatory cytokines and activates innate immune pathways, potentially leading to immunogenic cell death and reshaping the tumor microenvironment. Radiogenomic profiling has identified genomic alterations and molecular signatures associated with differential responses to SBRT and immune activation. These insights open avenues for precision radiotherapy approaches, including the use of genomic biomarkers for patient selection, the integration of SBRT with DDR inhibitors or immunotherapies, and the customization of treatment plans based on individual tumor genotypes and immune landscapes. Ultimately, these strategies aim to enhance SBRT efficacy and improve clinical outcomes through biologically tailored treatment. This review provides a comprehensive summary of current knowledge on the genetic determinants of response to stereotactic radiotherapy and discusses their implications for personalized cancer treatment. Full article

HSD3B1 encodes an enzyme that catalyzes the conversion of adrenal precursors into potent sex steroids. A common germline variant (c.1100C) enhances this effect and is linked to breast cancer (BC) progression. As the HSD3B1 genotypes contribute to differences in local and adrenal steroid production, their transcriptional and phenotypic effects on cancers influenced by hormonal signaling such as BC and endometrial cancer (EC)—particularly in relation to menopausal status—remain unclear. We analyzed BC and EC sequenced from patients that received diagnostic tests in oncology clinics, and we determined the germline HSD3B1 c.1100 genotype (AA, AC, CC) from tumor DNA sequencing by using variant allele frequency, with inferred menopausal status assumed by age at molecular profiling. Whole-transcriptome RNA sequencing and gene set enrichment analysis showed that adrenal-permissive homozygous (CC) tumors in premenopausal ER + BC were enriched for hormone-related pathways, including Estrogen Response Early (NES ≈ +1.8). In premenopausal triple-negative BC, adrenal-restrictive homozygous (AA) tumors exhibited the elevated expression of immune and epithelial genes and the increased prevalence of MED12 alterations (AA 0.25% vs. CC 8%, p < 0.01). In endometrioid EC, CC tumors demonstrated the suppression of immune and proliferative pathways. Postmenopausal cases had higher progesterone receptor IHC positivity (AA 75% vs. CC 83%, p < 0.05) and numerically more frequent ESR1 copy number gains (AA 2.0% vs. CC 4.0%). Results highlight context-specific associations between germline HSD3B1 genotypes and tumor biology in BC and EC. Full article

Human papillomavirus (HPV) is one of the most common sexually transmitted infections, affecting both men and women. However, in Serbia, the previous epidemiological and clinical research on HPV has primarily focused on women due to its established role in cervical cancer, while the data on HPV prevalence in men remain scarce. This study analyzed 634 samples from men (mean age: 30 years, SD = 9.98; range: 18–79) from between 2012 and 2024. Overall, 30.76% of the tested men were HPV–positive, with the highest percentage of cases being observed in those aged 25–29 years (32.82%). The most common genotypes were HPV 16 and HPV 31 (22.05% each), followed by HPV6 (20.51%), HPV 56, and HPV 52 (9.23% each). The prevalence of HPV was the highest in the samples from men with genital warts (40.77%). Among the available vaccines, the nonavalent Gardasil 9 provides the broadest protection, covering genotypes found in 82% of the HPV–positive cases identified in this study. Our findings underscore the importance of comprehensive HPV prevention and control measures for the male population, contributing to ongoing research efforts aimed at reducing the burden of HPV–associated diseases in our region. Increasing the vaccination coverage among Serbian men could substantially reduce the overall burden of HPV–related diseases in both sexes. Full article

Background: Colorectal cancer (CRC), the most common malignancy of the gastrointestinal tract, is the second leading cause of cancer-related deaths worldwide. In this context, investigating low-penetrance gene variants associated with the increased risk of CRC represents a novel and crucial approach to enhancing prevention strategies and clinical surveillance. By focusing on these genetic variants, there is potential for more accurate prediction of individual CRC risk, which could contribute to the refinement of current screening and prophylactic programs. The aim of this case–control study was to explore the association between SIRT1 polymorphisms and CRC risk. Methods: We analyzed three SNPs—rs12778366 (T/C), rs3758391 (C/T), and rs7895833 (A/G)—in the promoter region of the SIRT1 gene, which may influence SIRT1 expression and thus play a role in cancer development. Our study included 200 patients with colorectal adenocarcinoma and 115 controls. Genomic DNA was extracted from blood samples, and SIRT1 SNP analysis was performed using the qPCR method and endpoint genotyping. Results: Univariate regression analysis revealed a slightly increased risk of developing CRC in individuals with minor alleles of the analyzed polymorphisms; however, the observed differences were not statistically significant. Conclusions: Although our findings did not reveal statistically significant differences in SIRT1 gene polymorphism frequencies between the CRC group and the control group, we observed a tendency that suggests further investigation in larger cohorts is warranted. This research underscores the importance of understanding low-penetrance genetic factors in CRC, highlighting their potential to inform more personalized and effective prevention strategies. Full article

Multiple myeloma is a neoplastic disease characterised by the proliferation of clonal, atypical plasma cells. In cancer cells, the balance between two paths of cell death, necroptosis and apoptosis, is disrupted. The aim of this study was to analyse the occurrence of polymorphisms in genes encoding key proteins for the necroptosis process, i.e., RIPK-1, RIPK-3 and MAPKAPK2. We investigated the potential relations between the occurrence of genetic variability and the clinical course of the disease. We analysed six single-nucleotide polymorphisms in a population of patients with multiple myeloma (n = 205) and healthy volunteers (n = 100): RIPK1 rs2272990, RIPK1 rs9391981, RIPK3 rs724165, RIPK3rs3212243, MAPKAPK2, rs45514798 and MAPKAPK2 rs4073250. We found that genotypes rs9391981 CG, rs724165 CG, rs3212243 GG, and rs4073250 AA were independent predictors of overall survival, while genotype MAPKAPK2 rs4073250 AA was an independent predictor of progression-free survival. MAPKAPK2 rs45514798 AA was associated with polyneuropathy after thalidomide therapy. In conclusion, some of the SNPs tested have potential prognostic value and could be used as marker of survival in patients with multiple myeloma. Full article

Introduction: This study investigates the distribution and interaction of three polymorphisms—XRCC1 (rs1799782), CHEK2 (rs17879961), and XPD (rs238406)—in Romanian breast cancer patients, aiming to understand their association with histopathological subtypes, age, and BMI. Materials and Methods: This retrospective study analyzed 36 breast cancer patients from a Romanian clinic (2020–2024) with complete genetic data for XRCC1 (rs1799782), CHEK2 (rs17879961), and XPD (rs238406). The patients had invasive, non-metastatic breast cancer and no history of other cancers. Statistical analysis with Jamovi included descriptive stats, McNemar’s test for genotype associations, and multinomial logistic regression to explore links between variants, age, BMI, and tumor subtypes. Results: McNemar tests showed no significant association between XRCC1 and CHEK2 (p = 0.180), nor between XRCC1 and XPD (p = 0.03) or XPD and CHEK2 (p = 0.049) after applying the Bonferroni correction (α = 0.0167), indicating no statistically significant genetic dependency among these variants. A multinomial logistic regression model found that genetic variants, BMI, and age significantly predicted breast cancer subtypes, particularly CDI TNB. All predictors remained significant in the comparisons of CDI TNB vs. CDI LB/CDI LA. Notably, these associations remained unchanged even after applying the Bonferroni correction (α = 0.0021), confirming the robustness of the findings. Conclusions: This study identifies significant associations between XRCC1, CHEK2, and XPD gene variants and CDI TNB, suggesting a role of DNA repair deficiencies in its pathogenesis. Protective genotypes were under-represented in TNB cases. Limited links with luminal subtypes highlight TNB’s distinct genetic profile. Results support further research on these polymorphisms as markers for TNB risk and precision treatment. Full article

Background/Objectives: Accurately determining the bacterial bioburden that survives preoperative skin preparation (PSP) is critical in understanding PSP efficacy and its limitations. Clinical PSP approval relies on a bacterial sampling method described in the American Society for Testing and Materials (ASTM) standard E1173-15. Though common, this technique may overlook deep-dwelling skin bacteria. The objective of this study was to test the hypothesis that deep-dwelling skin flora would survive PSP, and more growth would be detected using a destructive sampling method compared with ASTM E1173-15. Methods: Twelve female participants with a scheduled deep inferior epigastric perforator (DIEP) artery flap procedure at the Huntsman Cancer Institute in Salt Lake City, UT, were enrolled between January and August 2024. PSP was performed using three 26 mL ChloraPrep applicators (2% CHG), and excess tissue was collected. Bacteria in the skin were quantified using a destructive sampling method and ASTM E1173-15, and bioburden outcomes were compared. Two participants were excluded from the quantitative analysis. Results: Bacteria survived PSP in every participant. A greater diversity and more bacteria were quantified with destructive sampling than ASTM E1173-15 (p < 0.01). Generally, anaerobic bioburden values were higher than aerobic bioburden values. Higher bioburden correlated with processing more skin from a participant. Genotypic identification of select isolates identified Staphylococcus epidermidis and Cutibacterium acnes (formerly known as Propionibacterium acnes) as surviving bacteria, among others. Immunofluorescence revealed bacteria in all skin layers. No participant exhibited clinical signs of infection in the abdominal region. Human data corroborated previous porcine data collected using destructive skin sampling after PSP. Conclusions: Clinical PSP application does not create a sterile field. Destructive skin sampling techniques may be more effective than ASTM E1173-15 at resolving bacterial PSP survivors contributing to SSI risk. Full article