Risk of clonal hematopoiesis in families exposed to radiation following the Chornobyl accident

Radiation exposure is a well-established risk factor for leukemia. Clonal hematopoiesis (CH), the expansion of mutated hematopoietic cells, is also associated with increased leukemia risk and its frequency is higher in cancer patients following radiotherapy and chemotherapy. We investigated whether low to moderate environmental ionizing radiation determined by state-of-the-art dosimetric analysis was associated with CH in the Chornobyl Family Study (CFS). Our study conducted targeted high-depth sequencing and array genotyping to identify and characterize clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) in 882 participants from 292 CFS families. Fathers had mean bone marrow radiation doses of 0.24 Gy (range: 0–3.86) and mothers had mean doses of 0.009 Gy (range: 2 × 10⁻⁵–0.63). The expected relationship between increasing age and CHIP was observed. No detectable effect of red bone marrow radiation dose was observed for CHIP risk (Fathers: Excess OR (EOR)/Gy = 0.41; 95% confidence interval (CI) = −0.57,1.39; P-value = .42; Mothers (categorical model due to limited dose range): odds ratio (OR)_{0.01–0.09 versus <0.001 Gy} = 0.73; 95% CI = 0.39,1.38; P-value = .33) and the distribution and types of CHIP and mCAs detected in CFS participants did not differ from that seen in previously published studies of unexposed populations. No transgenerational effect of parental gonadal radiation exposure was detected in the children (Fathers: P-value = .08; Mothers: P-value = .67). Our findings suggest the type and levels of radiation exposure investigated in CFS families are unlikely to be strong contributors to CH risk, which could have important implications for public health concerns following environmental exposure to low to moderate ionizing radiation.