Abstract PO-099: Racial differences in the association of circulating inflammatory proteins with mortality from causes other than the index cancer in older adult cancer survivors in the Atherosclerosis Risk in Communities (ARIC) study
Authors: Ugoji Chinenye C. , Dean Lorraine T. , Gross Alden , Platz Elizabeth A. 
Published: December 2020

Abstract
Background Inflammation is strongly hypothesized to underlie premature mortality in cancer survivors. However, little is known about racial differences in the associations of inflammatory proteins with premature mortality in cancer survivors. Methods 474 long-term (≥5 years) older adult survivors of prostate, breast, colorectal, endometrial and bladder cancers in the ARIC study were followed from visit 5 (2011-13) to December 2018. At visit 5, 5000 serum proteins were assayed using the high throughput SOMAscan technology. Using competing risks proportional hazards regression, we evaluated racial differences in the associations of 580 inflammatory proteins measured at visit 5 with deaths from causes other than the index cancer by modeling sub-distribution hazards (sHR) of deaths per log2 increase in each inflammatory protein in Black and White survivors. Models were adjusted for age, sex, race, years since cancer diagnosis, cancer/cardiovascular disease (CVD) shared risk factors such as smoking, history of CVD, diabetes, kidney function, and anti-inflammatory drug use, and included race-protein interaction terms. In a sensitivity analysis, we additionally adjusted for lifecourse SES and access to care. We accounted for multiple testing using Bonferroni correction and false discovery rate Q-values. Results Survivors were 21% Black, 56% male, had a mean age of 76.8 yrs, and median time since diagnosis of 11.4 yrs. 95 non-cancer (50% CVD) and 34 non- index cancer deaths occurred during 2740 person-years of follow-up. Thirty inflammatory proteins, 17 of these in the sensitivity analysis had significantly different (Q&lt;0.05) qualitative or quantitative effects in Black and White survivors. Inflammatory proteins with the most significant racial differences in the sHR of mortality were CD69 (early activation antigen), which was associated with lower mortality in Whites (sHR per Δlog2 (95% CI): 0.47 (0.27,0.82)) and higher mortality in Blacks (2.96 (1.78,4.93), Pint = 1.24 × 10-6], and CCL18 (CC motif chemokine 18), which was associated with higher mortality in Whites (1.83 (1.02,3.28)) and lower mortality in Blacks (0.33 (0.12 0.94), Pint = 4.14 × 10-3). The differential effect of CD69 by race remained significant after Bonferroni correction in the main and sensitivity analysis. Conclusion Associations of some circulating inflammatory proteins with mortality differ in Black and White cancer survivors independent of lifestyle, medical, and social factor confounders. CD69 is upregulated by NF-κB signaling and regulates a variety of crucial immune pathways that depend on host metabolic factors. CCL18 is mainly produced by the innate immune system and genetic variations in encoding genes have been reported. Further studies are needed to evaluate whether racial differences in host metabolic factors or genetic differences modulate effects of these proteins on mortality in Black and White survivors. If confirmed these proteins may warrant focus for characterization as potential therapeutic targets.
Citation Format: Chinenye C. Ugoji, Lorraine T. Dean, Alden Gross, Elizabeth A. Platz. Racial differences in the association of circulating inflammatory proteins with mortality from causes other than the index cancer in older adult cancer survivors in the Atherosclerosis Risk in Communities (ARIC) study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-099.