Abstract A017: Social, behavioral and clinical risk factors are associated with clonal hematopoiesis

Abstract 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. Understanding the interplay between these factors and preneoplastic hematopoietic expansion can provide insights into health disparities. Leveraging data from 485,028 UK Biobank participants without hematologic malignancies, our multivariable adjusted analyses reinforced smoking as a potent modifiable risk factor for multiple CH types where dose-dependent relationships with smoking-intensity and duration persisted post-cessation. Additionally, males in socially deprived areas of England had lower risk of mosaic loss of chromosome Y (mLOY) (OR = 0.997, 95%CI: [0.995-0.996], p = 4.88×10-7), females with moderate/high alcohol consumption (2-3 drinks/day) had increased mLOX risk (OR = 1.16, 95%CI: [1.086-1.24], p =1.21×10-5) compared to light drinkers, active males (moderate-high PA) had elevated risks of mLOY (PA Category 3: OR = 1.06, 95%CI: [1.03-1.088], p = 7.7×10-6) and men with high BMI (≥40) had reduced risk of mLOY (OR = 0.579, 95%CI: [0.515-0.65], p = 3.29×10-20). Sensitivity analyses with BMI adjustment attenuated the effect in the mLOY-PA associations (IPAQ2: OR = 1.037, 95%CI: [1.005-1.069], p = 2.13×10-2 and IPAQ3: OR = 1.036, 95%CI: [1.009-1.063], p = 7.77×10-3). Our study identified associations between CH, SD, smoking, alcohol consumption, and PA. As CH is an intermediate marker for hematologic cancer risk, our findings suggest social, behavioral and clinical exposures could contribute to common types of CH as well as potentially with rare hematologic cancers. Addressing these factors could be crucial in reducing hematologic cancer risk through clonal mechanisms and mitigating cancer disparities. Citation Format: Corey D. Young, Aubrey K. Hubbard, Pedro Saint-Maurice, Irenaeus Chan, Kelly L. Bolton, Stephen J. Chanock, Charles Matthews, Steven C. Moore, Erikka Loftfield, Mitchell J. Machiela. Social, behavioral and clinical risk factors are associated with clonal hematopoiesis [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A017.