Effects of Adverse Childhood Experiences, Allostatic Load, and Genetics on Risk of Breast Cancer

Biological embodiment is the process by which social experiences get under the skin. Adverse childhood experiences (ACEs) during key developmental periods have been demonstrated to impact long-term health outcomes by various mechanisms. ACEs may include any psychological, physical or sexual abuse, neglect, instability, and more. ACEs have been linked with an increase in risk factors such as smoking, alcohol consumption, and poor dietary habits. Additionally, changes in epigenetic profiles, inflammatory response, metabolic changes, and other physiological changes provide biological mechanisms by which disease risk may be influenced. Allostasis, the biological process by which our bodies accommodate stressful events, is increasingly being explored for its utility in predicting poor health outcomes. The allostatic load framework, which leverages measures of dysregulation across biological systems, may provide an objective measure for stress and adversity. The role that these two measures of stress and adversity play in chronic disease has been well established, however little evidence exists on their association with breast cancer risk. Using early life adversity data coupled with blood-based biomarkers from the UK Biobank, we assessed for associations between ACEs, AL, and breast cancer in females. We identified strong associations between reported ACEs and AL in adulthood in female participants of the UK Biobank, a finding that is consistent with existing literature. Our assessment of breast cancer as it relates to ACEs incorporated both prevalent and incident breast cancer cases, while associations with AL focused on incident BCa diagnoses (occurring after the biomarkers were collected.) We identified a null association between reported ACEs and breast cancer, though with a trend towards an inverse association. Effect modification by history of mammography was identified, indicating that non-screen detected breast cancers were more likely to be identified in women with a higher reported ACE burden. Positive associations between AL and breast cancer were observed, with a 3% increase in breast cancer risk with every one point increase in AL. Notably, this association was impacted by menopausal status at time of enrollment, with the association becoming negative in pre-menopausal women. Genetic risk as assessed by a validated polygenic risk score did not appear to modify the observed associations between either ACEs or AL and breast cancer.