Background/Objectives: Radiotherapy is a cornerstone in the treatment of breast cancer, yet its use is frequently accompanied by skin toxicities that vary in severity and timing among patients. The objective of this meta-analysis is to systematically evaluate the pooled impact of genetic variations on the risk and severity of acute and late skin side effects from radiotherapy in breast cancer patients. Materials and Methods: A systematic literature search was conducted across PubMed, Embase, and Scopus to identify studies published between 2014 and 2024 that examined associations between genetic polymorphisms and radiotherapy-induced skin toxicity. Studies were selected based on predefined inclusion and exclusion criteria, and data were synthesized using a random-effects meta-analysis model. The risk of bias was evaluated using the ROBINS-I tool, and publication bias was assessed through funnel plots and Egger’s test. Results: A total of 11 studies involving breast cancer patients were included, identifying associations between various gene polymorphisms and skin toxicity. The pooled analysis revealed that patients with specific genetic variants had a 53% increased risk of acute skin side effects and a 44% increased risk of late effects. Notable implicated genes included XRCC2, IFNG, ATM, TGFB1, and PER3. Significant heterogeneity and publication bias were noted across studies, warranting cautious interpretation. Conclusions: This meta-analysis highlights the role of genetic variation in predicting radiotherapy-induced skin toxicity in breast cancer patients. These findings support the future development of predictive biomarkers and personalized radiotherapy strategies to minimize treatment-related toxicity.

Human ageing and longevity are increasingly understood as biologically integrated and heterogeneous processes shaped by interactions among genetic susceptibility, epigenetic remodelling, and environmental modulation. This narrative review examines these interconnections within a nutrigenomic framework, with particular emphasis on how inherited variation and epigenetic plasticity may influence responses to ageing-related interventions. A structured literature search was conducted in PubMed, Scopus, Web of Science, and Embase, focusing on English-language studies published during the last 10 years. The review was organized into three major domains: (i) genetic determinants of longevity, (ii) epigenetic mechanisms of ageing, and (iii) intervention-responsive pathways relevant to precision geroscience. Current evidence supports a polygenic model of longevity in which loci such as FOXO3 and APOE show the most consistent human associations, while telomere maintenance, insulin/IGF-1 and mTOR signalling, sirtuins, Klotho, inflammatory mediators, and DNA repair remain biologically important but variably supported at the variant level. Epigenetic mechanisms, including DNA methylation drift, epigenetic clocks, histone modifications, chromatin remodelling, heterochromatin loss, and non-coding RNA regulation, provide an environmentally responsive interface linking genetic background to ageing phenotypes. Nutritional, pharmacological, behavioural, and circadian interventions converge on overlapping molecular pathways involving AMPK, mTOR, FOXO, sirtuins, autophagy, mitochondrial maintenance, and inflammatory signalling, although human evidence remains heterogeneous and biomarker modulation should not be equated with clinically meaningful slowing of organismal ageing. Overall, this review highlights the value of integrating genetics, epigenetics, and intervention biology to support a more cautious and translationally relevant model of healthy ageing. It also underscores the need for precision nutrigeroscience approaches that account for tissue context, baseline physiology, and inter-individual molecular variability.

Background. Breast cancer remains a leading cause of cancer-related death among women, with genetic mutations playing a key role. While high-penetrance mutations are well-studied, moderate-to-low-penetrance mutations, which present challenges in clinical decision-making and patient outcomes, are less understood. This study explores the quality of life of breast cancer patients with moderate-penetrance mutations, focusing on the psychosocial and physical consequences of mastectomy and reconstruction to improve patient-centered care. Materials and Methods. A cohort of 620 breast cancer patients treated at Regina Maria Private Health Network, Bucharest, between January 2022 and July 2024 was identified. From this group, 61 patients were selected based on the following criteria: (1) meeting NCCN genetic testing guidelines, (2) carrying moderate-to-low-penetrance mutations, (3) undergoing bilateral mastectomy with double reconstruction, and (4) agreeing to complete a modified version of the BREAST-Q questionnaire. Genetic testing was performed using a 125-gene next-generation sequencing panel. Statistical analyses included non-parametric tests to examine group differences and correlations. Results. Significant correlations were found between several factors. Emotional distress was positively correlated with concerns for family, while couple relationships and financial burden showed a strong positive association. Negative correlations were found between couple relationships and self-concept. Distress levels varied, with “Interference with personal relationships” causing more distress than “Impact on employment”, and financial burden causing more distressing than impact on sexuality. Conclusions. Prophylactic mastectomy significantly reduces cancer risk for women with moderate-penetrance mutations. This study highlights the relationship between surgical choices and quality-of-life factors, advancing personalized prevention strategies and emphasizing patient-centered care.

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.

Resistance to apoptosis, metabolic plasticity, and redox adaptation are major contributors to cancer progression and treatment failure. Ferroptosis and cuproptosis have therefore emerged as metal-dependent forms of regulated cell-death programs with potential relevance for tumours that survive conventional therapy. Ferroptosis is driven by iron-dependent phospholipid peroxidation when glutathione peroxidase 4 (GPX4)-dependent and parallel antioxidant systems fail, whereas cuproptosis depends on mitochondrial copper engagement of lipoylated tricarboxylic-acid-cycle proteins, lipoylated-protein aggregation, iron–sulfur protein destabilization, and proteotoxic stress. This review integrates the molecular basis, genetic architecture, long non-coding RNA (lncRNA)-mediated regulation, mechanistic crosstalk, and therapeutic implications of ferroptosis and cuproptosis in cancer. It emphasizes a critical evidence hierarchy: expression association, computational signature construction, metal accumulation, reactive oxygen species (ROS) generation, or reduced viability should not be interpreted as pathway dependency without pathway-defining biochemical endpoints and rescue experiments. The most credible translational opportunities will depend on functional stratification, tumour-selective delivery, and pharmacodynamic confirmation that distinguishes pathway-defined ferroptosis or cuproptosis from nonspecific metal-induced and oxidative cytotoxicity.

Somatic blood mosaicism is an established feature of ageing and a heterogeneous marker of haematologic cancer and inflammatory and vascular risk, but its psychiatric evidence base remains small. This structured critical narrative review evaluates mutation-defined clonal haematopoiesis, clonal haematopoiesis of indeterminate potential (CHIP), autosomal mosaic chromosomal alterations (mCAs), and sex-chromosome loss while separating probable developmental mosaicism from adult-acquired blood clonality. Direct human evidence comprises seven methodologically heterogeneous studies. Psychiatric CHIP findings rely mainly on one prospective UK Biobank cohort of 360,451 participants, in which CHIP was associated with any incident psychiatric disorder (hazard ratio 1.15), particularly major depressive and substance-use disorders. Separate studies report excess mosaic losses in schizophrenia and bipolar disorder and autosomal or X-chromosome mosaicism in suicide. Clone-size gradients and lesion-specific findings add biological structure, but do not provide independent replication. Most mechanistic support comes from cardiovascular, stroke and neurodegenerative research: mutant myeloid cells can alter inflammasome signalling, endothelial function, thrombosis and tissue macrophage behaviour. These pathways make indirect brain effects plausible without establishing a psychiatric mechanism. Blood detection also cannot date a mosaic event or demonstrate the same clone in neural tissue. Taken together, the available evidence supports somatic blood mosaicism as a potentially informative marker of psychiatric heterogeneity and shared inflammatory, vascular and ageing-related biology, but does not establish a causal blood-clone-to-brain pathway. Routine psychiatric screening for CHIP or mCAs is therefore not currently justified. The immediate research priority is independent replication in longitudinal cohorts with repeated sequencing, detailed exposure and treatment histories, and direct testing of inflammatory, vascular and neuroimaging intermediates capable of distinguishing cause, consequence and shared risk.