Exploring the nexus between ionizing radiation and breast cancer in silico mapping of the adverse outcome pathway

Abstract

Breast cancer, the most common malignancy in women, accounts for 36% of cancer cases, with its incidence rising, and ionizing radiation is one of the contributing risk factors. This study aimed to: investigate the link between breast cancer and ionizing radiation through in silico analysis, map the adverse outcome pathway connecting ionizing radiation to breast cancer, and propose additional key events to refine and enhance the adverse outcome pathway. The following publicly available databases, software, and tools were used: Comparative Toxicogenomics Database, ToppGene Suite, GeneMANIA server, and Metascape. Twenty identified genomic biomarkers (ATM, BARD1, BRCA1, BRCA2, CHEK2, E2F1, FBL, H2AX, HRAS, MDM2, RAD51, SIRT1, SNAI2, SFRP1, SFRP2, TANK, TP53, TRP53, TP53BP1, YAPI) were predominantly in physical interactions (57.48%), or belonged to the same pathway (19.99%), contributing to molecular functions associated with regulating cellular responses to DNA damage, double-strand break repair, and DNA integrity checkpoint signaling. These biomarkers exhibit binding capabilities to molecules such as p53, ubiquitin, transcription factors, and chromatin. These findings, combined with the existing breast cancer-ionizing radiation, provide a foundation for future research on ionizing radiation's molecular impact on breast cancer development, with biomarkers supporting early detection and prognosis.