Language

English

Publication Date

6-1-2026

Journal

Experimental Hematology

DOI

10.1016/j.exphem.2026.105420

PMID

41881101

PMCID

PMC13097147

PubMedCentral® Posted Date

4-22-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Clonal hematopoiesis of indeterminant potential (CHIP) is an age-related phenomenon associated with increased risk of hematologic malignancy. Preclinical studies have shown that infection is a driver of CHIP; clinical studies in people living with HIV suggest a relationship between chronic infection and CHIP, but the association between infection frequency and incident CHIP in the general population remains unknown. We leveraged the atherosclerosis risk in communities study to design a closed prospective cohort study. CHIP was determined based on whole-exome sequencing at 2 time points 20 years apart. Included were 3,367 individuals without cancer or CHIP at time 1 and without hematologic malignancy by time 2. The 3,367 study participants had an average age of 55.3 years at time 1; 59.1% were women, 40.9% were men; 24% were Black, and 76% were White. Documented infection was assessed from routinely collected hospital discharge summaries. Frequency was categorized as no documented infection, 1 infection, 2 infections, or ≥3 infections. Of the participants, 19.7% had incident CH, 6.9% had large CHIP, and 5.2% had large non-DNMT3A CHIP. Participants with ≥3 documented infections had an increased odds of incident CHIP (odds ratios [OR] 1.41, p = 0.03), especially large CHIP (OR 1.83, p = 0.008) and large non-DNMT3A CHIP (OR 1.81; p = 0.02). To our knowledge, this study is the first to demonstrate an association between infection and incident CHIP in a general population, highlighting a modifiable risk factor for CHIP. Further work is required to describe the mutation-specific impact underlying this observed relationship.

Keywords

Humans, Male, Female, Clonal Hematopoiesis, Middle Aged, Aged, Prospective Studies, Adult, Infections, Incidence, DNA Methyltransferase 3A, Hematologic Neoplasms, Risk Factors, Exome Sequencing, Infection, clonal hematopoiesis, CHIP, clonal hematopoiesis of indeterminate potential, infection frequency, incident CHIP

Published Open-Access

yes

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.