biostudies-literatureUsui YSpecial Postdoctoral Researcher Program at RIKENThe MSD Life Science FoundationThe Yasuda Medical FoundationThe Takeda Science FoundationThe Ministry of Education, Science, Sports, Culture, and Technology of JapanJapan Agency for Medical Research and Development (AMED)298-306https://www.ebi.ac.uk/biostudies/studies/S-EPMC12209765biostudies-literatureUnknown6(4)Clonal hematopoiesis of indeterminate potential (CHIP) has broad clinical relevance, and TP53 plays various roles within cells. However, the gene-specific and cross-disease significance of CHIP with TP53 mutations (TP53-CHIP) remains unclear. In this study, we evaluated TP53-CHIP using targeted sequencing data of 140,597 individuals without hematologic neoplasms in BioBank Japan. We identified 1,157 individuals with TP53-CHIP and clarified the characteristics of mutations and carriers. TP53-CHIP was associated with poor overall survival, especially because of lymphoid neoplasms and respiratory disease, in addition to myeloid neoplasms. Significant interactions accompanied by excess risks were observed between TP53-CHIP and lifestyle factors for disease-specific mortality: acetaldehyde expoBlood cancer discoveryClinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases.PMC1220976524K20206JP19kk0305010JP18km0605001JP22ama121015JP23tm062400223K19459JP23ck0106805Endo MIwasaki YMomozawa YIijima HUsui YMatsuda KNakagawa HfalseClinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases.Clonal hematopoiesis of indeterminate potential (CHIP) has broad clinical relevance, and TP53 plays various roles within cells. However, the gene-specific and cross-disease significance of CHIP with TP53 mutations (TP53-CHIP) remains unclear. In this study, we evaluated TP53-CHIP using targeted sequencing data of 140,597 individuals without hematologic neoplasms in BioBank Japan. We identified 1,157 individuals with TP53-CHIP and clarified the characteristics of mutations and carriers. TP53-CHIP was associated with poor overall survival, especially because of lymphoid neoplasms and respiratory disease, in addition to myeloid neoplasms. Significant interactions accompanied by excess risks were observed between TP53-CHIP and lifestyle factors for disease-specific mortality: acetaldehyde expo2025-01-01T00:00:00Z2025 Jul2026-06-02T17:52:47.911Z2026-04-18T03:11:59.137ZS-EPMC122097654052578610.1158/2643-3230.BCD-24-0355