{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:34:06Z","timestamp":1773286446333,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Acute radiotherapy-induced skin toxicity is a common complication in breast cancer treatment, with marked interindividual variability not fully explained by clinical factors. This study investigated the contribution of germline mutations in DNA repair and tumor suppressor genes to acute radiodermatitis in a homogeneous cohort treated with hypofractionated intensity-modulated radiotherapy with inverse planning, with adjustment for potential lifestyle confounders. Methods: Mutations were grouped into four functional categories: homologous recombination repair (HRR), Fanconi anemia (FA), DNA damage response (DDR), and tumor suppressor (TS) genes. Ordinal logistic regression models adjusted for clinical covariates evaluated pooled and functional category-specific mutation effects. Results: Overall, any mutation significantly increased the risk of higher-grade acute radiodermatitis (OR = 2.24, p = 0.003), an effect driven primarily by HRR and FA mutations, as exclusion of these mutations rendered the association non-significant (OR = 1.785, p = 0.064). Functional category-based analyses showed that HRR (OR = 2.60, p = 0.002) and FA (OR = 2.62, p = 0.002) mutations were the strongest predictors, reflecting overlapping roles in double-strand break and interstrand crosslink repair. DDR and TS mutations showed no significant effect. Conclusions: These results highlight the key role of high-fidelity DNA repair in normal tissue radiosensitivity and demonstrate that functional genetic stratification has diagnostic value as a pre-treatment predictive biomarker framework, enabling identification of patients at increased risk of acute skin toxicity and supporting personalized radiotherapy planning.<\/jats:p>","DOI":"10.3390\/diagnostics16060833","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:44:52Z","timestamp":1773229492000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Germline DNA Repair Mutations as Predictors of Acute Radiodermatitis in Breast Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Andreea","family":"C\u0103tan\u0103","sequence":"first","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Department of Oncogenetics, \u201cProf. Dr. I. Chiricu\u021b\u0103\u201d Institute of Oncology, 400015 Cluj-Napoca, Romania"},{"name":"Regional Laboratory Cluj-Napoca, Department of Medical Genetics, Regina Maria Health Private Network, 400363 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrada-Adelaida","family":"Belbe","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela Laura","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, \u201cProf. Dr. I. Chiricu\u021b\u0103\u201d Institute of Oncology, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hora\u021biu","family":"Ciliboaie","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, \u201cProf. Dr. I. Chiricu\u021b\u0103\u201d Institute of Oncology, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariela Sanda","family":"Militaru","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Regional Laboratory Cluj-Napoca, Department of Medical Genetics, Regina Maria Health Private Network, 400363 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina Ioana","family":"Iord\u0103nescu","sequence":"additional","affiliation":[{"name":"Genetic Centre Laboratory, Department of Medical Genetics, Regina Maria Health Private Network, 011376 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patriciu","family":"Achima\u0219-Cadariu","sequence":"additional","affiliation":[{"name":"1st Department of Oncologic Surgery, \u201cProf. Dr. I. Chiricu\u021b\u0103\u201d Institute of Oncology, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0975-5200","authenticated-orcid":false,"given":"Lorin-Manuel","family":"P\u00eerlog","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13014-023-02365-7","article-title":"Comparison of adverse events in partial- or whole breast radiotherapy: Investigation of cosmesis, toxicities and quality of life in a meta-analysis of randomized trials","volume":"18","author":"Haussmann","year":"2023","journal-title":"Radiat. 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