
PMID- 42550479
OWN - NLM
STAT- Publisher
LR  - 20260804
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Linking)
DP  - 2026 Aug 4
TI  - The joint association of clonal hematopoiesis of indeterminate potential and 
      biological aging with cancer risk among 332,911 individuals.
LID - djag268 [pii]
LID - 10.1093/jnci/djag268 [doi]
AB  - BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) and biological 
      aging have been individually associated with increased cancer risks. However, 
      their joint effect on cancer risks remains unknown. METHODS: We analyzed data 
      from 332,911 participants at baseline in the UK Biobank. We defined CHIP as a 
      pathogenic variant with variant allele fractions >/=2%. Biological aging was 
      assessed by the phenotypic age acceleration (PhenoAgeAccel) and categorized as 
      biologically younger and older. Associations of CHIP and biological aging with 25 
      cancers were assessed by Cox proportional hazard models. Interactions between 
      CHIP and biological aging were tested on additive and multiplicative scales. 
      RESULTS: CHIP was associated with higher risks of myeloid malignancies (HR 9.56, 
      95%CI 8.28-11.03), lung cancer (HR 1.61, 95%CI 1.42-1.82) and oesophageal cancer 
      (HR 1.54, 95%CI 1.18-2.01). Biologically older participants had higher risks of 
      hematologic neoplasms (HR 1.42, 95%CI 1.30-1.55) and various solid tumors 
      compared with biologically younger participants. CHIP carriers who were 
      biologically older had increased risks of hematologic neoplasms (HR 6.56, 95%CI 
      5.67-7.59) and various solid tumors compared with biologically younger 
      participants without CHIP. The proportion of excess risk attributable to additive 
      interaction was 40% for hematologic neoplasms and 27% for lung cancer. A 
      significant multiplicative interaction was also observed for hematologic 
      neoplasms (P  interaction<0.001). CONCLUSION: CHIP confers substantial cancer 
      risk, amplified when participants are biologically older. Assessing CHIP and 
      biological aging may serve as an effective strategy for early screening and risk 
      stratification for hematologic neoplasms and lung cancer.
CI  - (c) The Author(s) 2026. Published by Oxford University Press. All rights reserved. 
      For commercial re-use, please contact reprints@oup.com for reprints and 
      translation rights for reprints. All other permissions can be obtained through 
      our RightsLink service via the Permissions link on the article page on our 
      site-for further information please contact journals.permissions@oup.com.
FAU - Wang, Li
AU  - Wang L
AD  - Affiliated Mental Health Centre & Hangzhou Seventh People's Hospital, Zhejiang 
      University School of Medicine, Hangzhou, 310013, China.
FAU - Sun, Kaili
AU  - Sun K
AD  - The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 
      310058, Zhejiang, China.
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
FAU - Lu, Siqi
AU  - Lu S
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
FAU - Zheng, Yuyang
AU  - Zheng Y
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
FAU - Jia, Xueqing
AU  - Jia X
AD  - The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 
      310058, Zhejiang, China.
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
FAU - Zhao, Yanjie
AU  - Zhao Y
AD  - The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 
      310058, Zhejiang, China.
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
FAU - Shen, Lujia
AU  - Shen L
AD  - The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 
      310058, Zhejiang, China.
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
FAU - Zhang, Jingyun
AU  - Zhang J
AD  - Department of Epidemiology and Health Statistics, School of Public Health, 
      Hangzhou Medical College, Hangzhou 310059, Zhejiang, China.
FAU - Shao, Jing
AU  - Shao J
AD  - Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and 
      International School of Medicine, International Institutes of Medicine, Zhejiang 
      University, Zhejiang, China.
FAU - Tan, Xiao
AU  - Tan X
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
AD  - Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, China.
AD  - Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
FAU - Sun, Jie
AU  - Sun J
AD  - Department of Hematology, The First Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou, Zhejiang, China.
AD  - Zhejiang Key Laboratory for Precision Diagnosis and Treatment of Hematological 
      Malignancies, Hangzhou, Zhejiang, China.
AD  - Zhejiang Provincial Clinical Research Center for Hematological Disorders, 
      Hangzhou, Zhejiang, China.
FAU - Liu, Zuyun
AU  - Liu Z
AD  - The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 
      310058, Zhejiang, China.
AD  - Department of Big Data in Health Science, School of Public Health, Zhejiang 
      University School of Medicine, Zhejiang Key Laboratory of Intelligent Preventive 
      Medicine, Hangzhou 310058, Zhejiang, China.
LA  - eng
PT  - Journal Article
DEP - 20260804
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
SB  - IM
EDAT- 2026/08/04 12:46
MHDA- 2026/08/04 12:46
CRDT- 2026/08/04 11:33
PHST- 2025/12/08 00:00 [received]
PHST- 2026/05/08 00:00 [revised]
PHST- 2026/07/17 00:00 [accepted]
PHST- 2026/08/04 12:46 [medline]
PHST- 2026/08/04 12:46 [pubmed]
PHST- 2026/08/04 11:33 [entrez]
AID - 8751166 [pii]
AID - 10.1093/jnci/djag268 [doi]
PST - aheadofprint
SO  - J Natl Cancer Inst. 2026 Aug 4:djag268. doi: 10.1093/jnci/djag268.
