JAMA Oncol. 2026 Jan 8. doi: 10.1001/jamaoncol.2025.5785. Online ahead of print.
ABSTRACT
IMPORTANCE: Cancer survivors have increased cardiovascular disease (CVD) risk partly due to the toxic effects of cancer therapy. Clonal hematopoiesis of indeterminate potential (CHIP), an age-associated blood disorder caused by somatic variants in blood stem cells, is more prevalent among individuals receiving cancer therapy and increases CVD risk independent of traditional risk factors. It is unknown whether CHIP amplifies therapy-related cardiovascular toxic effects in patients with cancer.
OBJECTIVE: To assess the association between CHIP and CVD risk, accounting for competing risks, among patients with primary solid tumors who received chemotherapy, radiotherapy, or immunotherapy.
DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted using BioVU, Vanderbilt University Medical Center’s biorepository linking electronic health records to whole-genome sequencing data from 250 038 participants from 2006 to 2025. In this cohort, participants had a primary solid tumor diagnosis, received chemotherapy, radiotherapy, and/or immunotherapy, and did not have hematologic malignant disease before treatment. Data were analyzed from June 2025 to November 2025.
EXPOSURES: CHIP variants detected via whole-genome sequencing, chemotherapy, radiotherapy, and immunotherapy.
MAIN OUTCOMES AND MEASURES: Time to first cardiovascular event, defined as heart failure, ischemic CVD, or arrhythmia following cancer treatment.
RESULTS: Among 8004 eligible participants (median [IQR] age, 61.9 [52.2-69.9] years; 4385 female individuals [54.8%]) with a primary solid tumor diagnosis, 7438 had no heart failure, 7392 no ischemic CVD, and 6002 no arrhythmia before cancer therapy. Overall, 549 (6.9%) had CHIP. In the propensity score-matched cohort, participants with CHIP had a significantly higher 10-year cumulative incidence of heart failure (20.3%; 95% CI, 16.0%-24.4% vs 14.5%; 95% CI, 13.5%-15.6%; P = .001) and ischemic CVD (25.3%; 95% CI, 20.5%-30.0% vs 18.5%; 95% CI, 17.3%-20.0%; P < .001) compared with those without CHIP. In adjusted Fine-Gray models, CHIP was associated with increased risk of heart failure (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.56; P = .03). In an exploratory 24-month landmark analysis, there was a statistically significant interaction between CHIP and intensive chemotherapy (≥7 cycles) on heart failure risk (sHR, 1.02; 95% CI, 1.00-1.04; P = .03).
CONCLUSIONS AND RELEVANCE: In this cohort study, CHIP was associated with increased CVD risk in patients with solid tumors receiving cancer therapy. This finding suggests incorporating CHIP status may improve cardio-oncology treatment of cancer survivors.
PMID:41505144 | DOI:10.1001/jamaoncol.2025.5785
