Abstract PS3-02-20: Epidemiological study of BRCA1 and BRCA2 mutations in a post-nuclear disaster region: A retrospective cohort of 136 breast cancer patients in Fukushima, Japan

Abstract Background: Despite global interest in radiation and cancer risk, no prior study has systematically evaluated the clinical-genetic features of breast cancer in a nuclear disaster zone. This is the first real-world investigation of BRCA1/2 germline mutations in a radiation-affected population—Fukushima, Japan—following the 2011 Daiichi nuclear accident. Understanding hereditary breast cancer in this context is essential for global oncology and disaster medicine. In Japan, the reported prevalence of pathogenic BRCA1/2 variants among clinically tested breast cancer patients typically ranges from 10% to 15%. Whether radiation exposure alters this background frequency remains unknown. Methods: A retrospective cohort study was conducted on 136 breast cancer patients who underwent BRCA1/2 genetic testing under national insurance coverage between July 2020 and December 2024 at our institution, located 20-70 km from the Fukushima Daiichi nuclear power plant. All patients met clinical testing criteria (e.g., early-onset, TNBC, family history, multiple primary tumors). Clinical and pathological data were compared between BRCA-positive and BRCA-negative groups. Predictors were evaluated via Poisson regression analysis. Results: Pathogenic BRCA1/2 variants were detected in 25 patients (18%; BRCA1: 10, BRCA2: 15). The mutation spectrum showed no radiation-specific signatures. Median age at diagnosis was 49 years. Among BRCA carriers, 48% were PgR-negative, and 28% had TNBC under age 60. Univariate analysis revealed significant associations between BRCA positivity and PgR-negativity (IRR = 2.77, p = 0.003), multiple primary tumors (IRR = 2.39, p = 0.018), and early-onset TNBC (IRR = 3.14, p = 0.001). Multivariate analysis confirmed that multiple primary tumors were an independent predictor (IRR = 2.30, p = 0.009). Conclusion: This is the first-ever genetic epidemiology study of hereditary breast cancer conducted in a radiation-affected human population. Despite proximity to the Fukushima nuclear accident, the BRCA mutation frequency (18%) in this cohort was within or slightly above the national average reported in non-exposed Japanese populations, with no evidence of radiation-induced variant types. Our data suggest that environmental radiation had limited impact on BRCA-driven tumorigenesis. Importantly, the independent predictive value of multiple primary tumors supports refined HBOC screening strategies. This study provides a globally unique model for integrating disaster exposure, genetics, and precision oncology—and demonstrates that high-quality hereditary cancer care is feasible even in post-disaster contexts. Citation Format: K. Gonda, A. Ozaki, A. Hara, M. Murakami, Y. Kaneda, A. Ajitomi, M. Wada, T. Sawano, T. Kurokawa, Y. Tamada, M. Tsubokura, M. Okano, K. Tachibana, S. Saji, T. Ohtake. Epidemiological study of BRCA1 and BRCA2 mutations in a post-nuclear disaster region: A retrospective cohort of 136 breast cancer patients in Fukushima, Japan [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-20.