Guha - Population Science Project

Cardiovascular disease (CVD) and cancer often occur in the same patients, in part because of shared risk factors such as obesity. As compared with European Americans (EAs), the prevalence of obesity is higher in African Americans (AAs) who in turn suffer from a higher burden of CVD and cancer-related mortality. The mechanisms whereby risk factors such as obesity change the natural history of cancer development in AAs with CVD remain to be determined. Identifying these mechanisms will facilitate prevention, screening, and perhaps therapeutic approaches. Socioeconomic disparities due to systemic racism, chronic psychosocial stress, and lack of access to affordable, high-quality food and healthcare may promote obesity. The resulting pro-inflammatory milieu is a significant risk factor for CVD and cancer, thus contributing to the higher burden of CVD and cancer in AAs. Additionally, biological factors that regulate systemic inflammation may be contributory. Mutations in ACKR1, otherwise known as the Duffy antigen receptor for chemokines (DARC), confer protection against malaria, and ~70% of AA express a mutation in this receptor resulting in loss of its expression on red blood cells. This loss of DARC expression, a chemokine receptor that sequesters chemokines and diminishes chemokine receptor activation, may contribute to the enhanced inflammation in AAs. AAs exhibit more pronounced inflammation than EAs, even when normalized to body mass index. Our group data in a murine model indicates that global DARC gene deletion augments obesity-related metabolic disease and inflammation. We hypothesize that obesity and socioeconomic disparities, coupled with the loss of DARC, lead to augmented inflammation, thus predisposing AAs with CVD to cancer development. This hypothesis will be tested in longitudinal population studies that enroll large numbers of AAs.Aim 1: Test the hypothesis that amongst both EAs and AAs, obese patients with CVD are at a higher risk for cancer development, driven in part by social inequalities and health disparities that augment obesity. For this aim, the ARIC-Cancer cohort, NHANES-Medicare cohort, and a newly created NCDR CathPCI-Medicare merged registry will be used. Aim 2: Test the hypothesis that inflammation and reduced DARC expression predicts cancer development in AA patients with CVD. The ARIC-Cancer cohort and the NHANES-Medicare cohort will be used for this aim.