Risk of Clonal Hematopoiesis of Indeterminate Potential after Cancer Radiation Therapy

Clonal hematopoiesis of indeterminate potential (CHIP) is a condition associated with aging and increased risk of hematologic malignancies and chronic diseases. While radiation therapy (RT) has been implicated as a risk factor for CHIP, the specific radiation parameters influencing the development of CHIP remain unclear. This study aimed to investigate the association between RT and CHIP and identify relevant radiation parameters affecting CHIP risk. We conducted a retrospective cohort study of cancer patients with RT exposure from an institutional biobank. DNA sequencing was performed to detect mutations in 22 CHIP-associated genes. Multivariable logistic regression models were used to evaluate the association between clinical characteristics, RT parameters, and CHIP. We identified 736 cancer patients with RT exposure and compared their risk of CHIP to a control cohort of 13,605 individuals. RT was found to be an independent risk factor for developing CHIP (OR 1.39, 95% CI 1.08-1.77, p=0.009). The prevalence of CHIP in RT patients was 22.8%. Compared to controls, RT patients showed significantly increased mutations in DNMT3A , PPM1D , TP53, and BRCC3. A positive correlation was observed between CHIP risk and biological equivalent dose of radiation. Stereotactic radiation was also associated with increased CHIP prevalence (OR 2.24, 95% CI 1.14-4.33, p=0.02). This study demonstrates that RT is associated with an increased risk of CHIP development, particularly mutations in DNA damage response genes. These findings have important implications for cancer care and long-term patient monitoring, emphasizing the need for further research into the mechanisms and consequences of RT-related CHIP.