New paper identifies CDH13 as a genetic determinant of cellular sensitivity

30. July 2026

Radiotherapy is one of the most widely used treatment modalities in oncology, yet individual differences in normal tissue radiosensitivity remain poorly understood and difficult to predict. A new collaborative study led by Hannah-Lena Schmidt and long-time BASE-II collaborator  Dr. Ilja Demuth (Charité Berlin), with Olena Ohlei and Lars Bertram contributing from LIGA, now reports the first genome-wide association study (GWAS) of cellular sensitivity to ionizing radiation (IR) and mitomycin C (MMC) in lymphoblastoid cell lines (LCLs) derived from older male participants of the Berlin Aging Study II (BASE-II). To this end, viability data from 137 (IR) and 140 (MMC) LCLs, quantified as the area under dose-response curves (AUC) were used as quantitative phenotypes in GWAS analyses. For IR sensitivity, the study identified a genome-wide significant association with a rare intronic variant in CDH13 on chromosome 16q23.3. CDH13 encodes cadherin 13 (T-cadherin), an atypical GPI-anchored member of the cadherin superfamily that protects vascular endothelial cells from oxidative stress-induced apoptosis and functions as a tumor suppressor — both properties highly plausible in the context of cellular IR response. Polygenic scores derived from cancer-related GWAS in the UK Biobank explained approximately 5% and 3% of phenotypic variance in IR- and MMC-induced cell viability, respectively, providing independent support for a genetic component underlying cellular mutagen sensitivity. The paper was published open-access in the International Journal of Molecular Sciences and is available at https://doi.org/10.3390/ijms27156826.