Abstract A16: Longitudinal evaluation of cancer-associated biomarkers before and after weight loss: Implications for cancer risk reduction

Abstract

Abstract Introduction: Obesity is a major risk factor for the development of endometrial cancer (EC). An improved understanding of biologic mechanisms associated with weight loss may guide preventive strategies for EC development. The goal of this study was to explore longitudinal biomarker changes in obese women who lost weight by participating in the Re-Energize with Nutrition, Exercise and Weight Loss (RENEW) study. We hypothesized that intentional weight loss may reduce EC risk through modification of biomarkers related to inflammation, hormonal balance, and cancer antigens. Methods: Serum samples from 89 participants with Class II and Class III obesity (mean body mass index (BMI) = 43.84 ± 5.4 kg/m2, total body fat = 58.5 ± 10.4%) were obtained in the RENEW study. Samples were also obtained from a comparison group of 43 controls representing lean, overweight, and class I obese subjects, measured once at baseline. Twenty-one bead-based xMAP immunoassays were utilized in this study: cancer-associated antigens 125 and 15-3, carcinoembryonic antigen (CEA), interleukins (IL) 2, 6, 7, 8, 10, IL-receptor 1alpha, tumor necrosis factor alpha (TNF-a), insulin-like growth factor binding proteins (IGFBP) 1 and 2, vascular endothelial growth factor (VEGF), eotaxin, soluble E-selectin, thyroid stimulating hormone (TSH), prolactin, growth hormone (GH), resistin, adiponectin, and insulin like growth factor 1 (IGF-1). Biomarker expression was analyzed at the Luminex Core Facility at the University of Pittsburgh Cancer Institute. Linear regression was used to evaluate the association between baseline BMI and biomarker expression adjusted for age, race, and smoking status. A one-way repeated measures analysis of variance was used to examine the association between changes in biomarker expression levels over time (baseline, 6 months and 12 months). Linear mixed effects models were used to examine longitudinal relationships between biomarker expression levels, BMI, steps, and time period adjusting for age, race, and smoking status. Results: Participants in the RENEW study lost an average of 12.8 kg from baseline to the 12 month assessment, with the largest change occurring in the first 6 months of the intervention. Mean levels of VEGF, soluble E-selectin, GH, adiponectin, IL-6, IL-7, CA-125, and IGFBP-1 significantly differed between time periods. In adjusted mixed linear models, decreasing BMI was significantly associated with decreased in soluble E-selectin and IL-6 and increases in GH, adiponectin, and IGFBP-1. Conclusions: This is one of the first efforts to explore changes in cancer-associated biomarkers in a cohort of weight loss research participants at high risk for EC development. This work adds to the current literature in several fields including endometrial cancer biomarkers, physical activity, and weight loss, and has significant potential implications for EC prevention. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A16.