A Nutrition and Exercise Prehabilitation Intervention on Inflammatory Biomarkers in American Indian Cancer Patients

PROJECT ABSTRACT There are 13 cancer subtypes that are linked to obesity and these account for 40% of all cancers diagnosed in the United States annually. American Indian/Alaska Native (AI/AN) populations are 1.6 times more likely to be obese than the general population. Many factors influence this elevated risk including poverty, nontraditional foods, related social determinants of health, and physical inactivity. Furthermore, AI/AN people have the worst cancer survival rates of any US racial group. Obesity-related inflammation likely drives cancer risk and adverse outcomes, and yet, this is a reversible process. AI/AN are known to be underrepresented in clinical trials and research, and even more importantly, they have never been included in an intervention designed to modulate inflammation prior to cancer surgery. A small handful of studies in non-AI/AN featuring lifestyle interventions following diagnosis of obesity-related cancer and implemented during the short window of opportunity (WOO) before cancer surgery, a strategy known as prehabilitation (prehab), have shown some significant findings. These include alterations in the expression levels of inflammatory markers in serum and the tumor microenvironment (TME), factors that may influence carcinogenesis. Given the higher prevalence of obesity and worse cancer outcomes, the AI/AN population may have the greatest gains from this line of research. We hypothesize that a prehab intervention modeled after published literature then adapted with community collaboration for AI cancer patients will be feasible, acceptable, and successful at modulating inflammatory biomarkers. The proposed project is to (1) complete the adaptation of a prehab intervention using the candidate’s preliminary research, (2) implement the prehab translational clinical trial for AI patients with obesity-related solid tumor cancer preparing for surgery, and (3) measure inflammatory biomarkers pre and post-intervention to assess responsiveness. Study outcomes include pre and post comparisons of serum biomarkers (insulin, leptin, hsCRP, IL-6, TNFα, cortisol AM, prealbumin); tissue biomarkers (Ki67, insulin receptor, TNFα, NFκB, NOS2, cleaved caspase-3); anthropometric measurements (blood pressure, weight, waist circumference); lifestyle behavioral measures (validated diet/exercise tools: REAPS, IPAQ, 6MWT, STS). The proposed training plan builds on the applicant’s background in surgical oncology, public health, and AI/AN cancer disparities to include new training in (a) clinical trial design and implementation, (b) biomarker measurement and (c) professional development. The rigorous research and training strategies will promote the candidate’s goal of successfully transforming into an independent, funded translational clinical trialist working on behalf of AI/AN to narrow cancer disparities. This will be achieved with the support of a highly experienced mentorship team and the well-resourced training environment of The University of Arizona, an AI/AN-serving institution and home to the only NCI-designated Comprehensive Cancer Center in the state of Arizona.