Abstract
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.