Abstract 1771: Metabolic dysregulation and cancer mortality in a national cohort of African-Americans and whites

Introduction: Complex biological pathways link metabolic dysregulation (obesity, hypertension, dyslipidemia and diabetes) with cancer tumorigenesis, progression and metastasis, and those include higher circulating insulin, chronic inflammation, and increased visceral fat stores and estrogen. In this study, we examine the association between metabolic dysregulation and cancer mortality in a racially diverse cohort of adults. Methods: A total of 25,038 African-American and White adults recruited through the prospective Reason for Geographic and Racial Disparities in Stroke (REGARDS) study were included in this study. Socio-demographics, medical history, and biomarkers (including blood pressure, fasting blood glucose, C-reactive protein, HDL and LDL cholesterol, height, weight, waist and hip measurements) were assessed at baseline. Metabolic dysregulation was defined in two ways: 1) based on Alberti et al. (2009) criteria of at least three of: high blood pressure, elevated triglycerides, reduced HDL cholesterol, elevated fasting blood glucose and high BMI; and 2) factor analysis of 15 variables indicative of metabolic abnormalities, including BMI, diabetes, triglycerides, total cholesterol, diastolic and systolic blood pressure, and fasting blood glucose. Cox proportional hazards regression analysis was used to model the hazards of cancer mortality in relation to each individual component as well as the cluster of metabolic dysregulation. Results: About 51% of African-American females, 38% of African-American males, 38% of White females and 40% of White males met the joint criteria for metabolic dysregulation. White females in the highest quartile of the factor associated with high fasting blood glucose and diabetes experienced a 2-fold increase in cancer mortality (HR: 2.02, 95% CI: 1.27 - 3.20) compared to those in the lowest quartile. In crude analysis, elevated HDL cholesterol (HR: 1.16, 95% CI: 1.02 - 1.31), elevated blood pressure (HR: 1.33, 95% CI: 1.15 - 1.54), and elevated fasting blood glucose (HR: 1.23, 95% CI: 1.09 - 1.40) were each associated with higher mortality, although these associations were attenuated after adjusting for gender, race, age, and SES. However, in the fully adjusted model, having at least three of the five metabolic dysregulation components was associated with a 46-61% increased hazard of cancer-related death compared with having none (HR for 5 components: 1.61, 95% CI: 1.02 - 2.55). Conclusion: There are marked racial differences in the prevalence of metabolic dysregulation, and the strong association with cancer mortality suggests that this may be a major factor in the observed and persistent disparities in cancer mortality. Metabolic abnormalities are highly modifiable through lifestyle changes and medication; appropriate prevention strategies have significant potential to reduce the risk of tumor metastasis, recurrence and death. Citation Format: Tomi Akinyemiju, Justin X. Moore, Suzanne Judd, Monika Safford, Maria Pisu. Metabolic dysregulation and cancer mortality in a national cohort of African-Americans and whites. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1771.