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Among them, 1,157 carriers were identified and mutation and carrier characteristics were characterized. TP53-CHIP was linked to worse overall survival, with added emphasis on lymphoid neoplasms and respiratory disease beyond myeloid neoplasms. Interactions with lifestyle factors shaped disease-specific mortality, including acetaldehyde exposure via ALDH2 and smoking for respiratory outcomes. Effects could remain partly independent of variant allele fractions, supporting personalized risk management.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/clinical-significance-of-tp53-mutant-clonal-hematopoiesis-across-diseases-research-brief/376181/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/clinical-significance-of-tp53-mutant-clonal-hematopoiesis-across-diseases-research-brief/376181.png","ImageObject",300,407,{"name":92,"@type":93},"McQueen","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How was TP53-CHIP evaluated in the study?","Question",{"text":113,"@type":114},"The study used targeted sequencing data from 140,597 BioBank Japan individuals without hematologic neoplasms, then identified carriers with TP53-CHIP.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What clinical outcomes were associated with TP53-CHIP?",{"text":118,"@type":114},"TP53-CHIP was associated with poorer overall survival, particularly related to lymphoid neoplasms and respiratory disease in addition to myeloid neoplasms.",{"name":120,"@type":111,"acceptedAnswer":121},"Which lifestyle factors showed interactions with TP53-CHIP for mortality?",{"text":122,"@type":114},"Acetaldehyde exposure linked to drinking and the ALDH2 germline variant was associated with myeloid neoplasm mortality, and smoking showed interactions for respiratory disease mortality.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},376181,1790270311,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},5909890329169,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","ReseaRch BRief  \nClinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases   \nYoshiaki Usui1, Mikiko Endo1, Yusuke Iwasaki1, Hanae Iijima1, Hidewaki Nakagawa2, Koichi Matsuda3, and Yukihide Momozawa1  \nClonal hematopoiesis of indeterminate potential (CHIP) has broad clinical rele  \nvance, 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 exposure (resulting from the interaction between drinking and the germline variant of ALDH2) for myeloid neoplasms and smoking for respiratory disease. The clinical significance of TP53-CHIP was sometimes largely independent of variant allele fractions. These findings elucidate aspects of disease pathogenesis and inform personalized risk management.  \nSignifiCAnCe: TP53-CHIP contributed to a wide range of outcomes besides myeloid neoplasm mortality. TP53-CHIP, when combined with environmental factors, showed a remarkably higher risk for disease-specific mortality, accompanied by excess risks.  \n1Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 2Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 3Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.  \nY. Usui andY. Momozawa contributed equally as co-corresponding authors. Corresponding Authors: Yoshiaki Usui, Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho,  \nTsurumi-ku, Yokohama 230-0045, Japan. E-mail: [yoshiaki.usui@riken.jp](yoshiaki.usui@riken.jp); and Yukihide Momozawa, [momozawa@riken.jp](momozawa@riken.jp)  \nBlood Cancer Discov 2025;6:298–306  \ndoi: 10. 1158/2643-3230 . BCD-24-0355  \nThis open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.  \n©2025 The Authors; Published by the American Association for Cancer Research  \ninTRoducTion  \nClonal hematopoiesis of indeterminate potential (CHIP) is commonly defined as clonally expanded somatic mutations of variant allele fractions (VAF) to 2% or more in multiple blood lineages or in hematopoietic stem cells in the absence of hematologic neoplasms (1) . It has a wide clinical significance, including an association with the risk of myeloid neoplasms (1). Furthermore, it is frequently encountered in the clinical sequencing for individuals with cancer (2). The molecular and clinical consequences of somatic mutations differ depending on the genes affected, suggesting that a gene-specific approach is often more informative than broad categorizations (3). Evaluating CHIP at the gene level alongside clinical data has the potential to enhance risk assessment and clarify disease mechanisms. Moreover, integrating evidence across diseases is crucial for providing comprehensive carrier management.  \nThe TP53 gene encodes the p53 tumor suppressor protein, which is commonly referred to as the “Guardian of the Genome”(4) . TP53 plays various roles within cells, and its mutation causes various alterations in hematopoietic stem and progenitor cell function (1) . Although TP53 is a biologically important gene and is often affected in CHIP, its clinical relevance beyond myeloid neoplasms (1, 5) and cancer treatment (","cbCaiv5VpNuGN6w7","https://ap.wps.com/l/cbCaiv5VpNuGN6w7","pdf",6611483,"English","# Introduction\n# Results\n## Cohort Description\n## Detection of TP53-CHIP","[{\"question\":\"How was TP53-CHIP evaluated in the study?\",\"answer\":\"The study used targeted sequencing data from 140,597 BioBank Japan individuals without hematologic neoplasms, then identified carriers with TP53-CHIP.\"},{\"question\":\"What clinical outcomes were associated with TP53-CHIP?\",\"answer\":\"TP53-CHIP was associated with poorer overall survival, particularly related to lymphoid neoplasms and respiratory disease in addition to myeloid neoplasms.\"},{\"question\":\"Which lifestyle factors showed interactions with TP53-CHIP for mortality?\",\"answer\":\"Acetaldehyde exposure linked to drinking and the ALDH2 germline variant was associated with myeloid neoplasm mortality, and smoking showed interactions for respiratory disease mortality.\"}]","Clinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases - Research Brief | PDF",1790217629,23]