Social Genomics Model of Health Disparities.

Structural racism and racial discrimination (SRD) extract enormous health and societal costs, decreasing access to cancer care and increasing health disparities, especially among the most vulnerable. For instance, although they face heightened lung cancer risk, Black Americans with lung cancer are 16% less likely to be diagnosed early, 19% less likely to receive surgical treatment, and 7% more likely not to receive any treatment compared to White Americans. When treatment is received, adverse events experienced by Black patients are less likely to be recognized and addressed by providers. Furthermore, societal factors appear associated with outcomes for these individuals. Heightened racial segregation increases lung cancer stage and mortality only for Black patients. Racial animus-as measured by the frequency of racial slur Google searches in a community-has a stronger association with overall mortality among Black persons than does poverty. An individual's personal experience of discrimination correlates with worse health status. Despite these observations, evaluations of lung cancer outcomes have largely overlooked SRD complexity and the potential for structural (e.g. residential segregation), sociocultural (e.g. racial animus) and attitudinal (personal experience of discrimination) domains to amplify the outcomes gap. Further, the biological link through which SRD exposures produce disparities is missing. Emerging models of health outcome inequities examine social and cultural factors such as SRD and its influence on gene expression and physiologic dysfunction over time. This area of research is termed social genomics and uses a biobehavioral pathway for cancer development and outcomes. Conserved transcriptional response to adversity (CTRA), an example of a stress transcriptome, comprises 53 proinflammatory and antiviral genes associated with adverse living conditions and worse cancer outcomes. Allostatic load incorporates 15 common laboratory and clinical values (e.g., hemoglobin A1C) that capture physiologic dysregulation in the immune, cardiac and metabolic systems from external stressors. In general, Black persons have a higher allostatic load than do White persons. In Black women with breast cancer, allostatic load correlates with worse tumor features; CTRA expression is associated with higher morbidity and mortality. Higher allostatic load correlates with patient-reported high pain levels prior to initiation of myeloma induction therapy and may be associated with reduced treatment tolerability, defined as one's capacity to continue cancer treatment given its adverse effects. We summarize a novel model for health outcomes gaps that capture a complex interplay between behavioral risk, external stressors including SRD, and stress response.