Background: Risk factors including smoking, alcohol intake, physical activity (PA), and sleep patterns have been associated with cancer risk. Clonal hematopoiesis (CH), including mosaic chromosomal alterations (mCAs) and clonal hematopoiesis of indeterminate potential (CHIP), is linked to increased hematopoietic cancer risk, and could be used as common pre-clinical intermediates for better understanding associations of risk factors with rare hematologic malignancies.
Methods: We analyzed cross-sectional data from 478,513 UK Biobank participants without hematologic malignancies using multivariable adjusted analyses to assess the associations between lifestyle factors and CH types.
Results: Smoking was reinforced as a potent modifiable risk factor for multiple CH types, with dose-dependent relationships persisting post-cessation. Males in socially deprived areas of England had lower risk of mosaic loss of chromosome Y (mLOY), females with moderate/high alcohol consumption (2-3 drinks/day) had increased mLOX risk (OR=1.17, 95%CI:[1.09-1.25], p=8.31×10-6) compared to light drinkers, active males (moderate-high PA) had elevated risks of mLOY (PA Category 3: OR=1.06, 95%CI:[1.03-1.08], p=7.57×10-6) and men with high BMI (≥40) had reduced risk of mLOY (OR=0.57, 95%CI:[0.51-0.65], p=3.30×10-20). Sensitivity analyses with BMI adjustment attenuated the effect in the mLOY-PA associations (IPAQ2: OR=1.03, 95%CI:[1.00-1.06], p=2.13×10-2 and IPAQ3: OR=1.03, 95%CI:[1.01-1.06], p=7.77×10-3).
Conclusions: Our study reveals associations between social deprivation, smoking, alcohol consumption, and CH risk, suggesting these exposures could contribute to common types of CH and potentially rare hematologic cancers.
Impact: This study underscores the impact of lifestyle factors on CH frequency, emphasizing social, behavioral, and clinical influences and the importance of socio-behavioral contexts when investigating CH risk factors.