Abstract OBJECTIVE Obesity, increasingly recognized to be associated with low-grade systemic inflammation, is a global pandemic that has been linked to several forms of malignancies, including breast, colon, and endometrial cancer (EC). The goal of this study was to explore longitudinal inflammatory biomarker changes in overweight and obese participants of the SMART and PREFER behavioral weight loss trials, focusing on participants who were most successful in reducing body mass index (BMI) by the 12th month of the intervention. We hypothesized that overweight and obese individuals undergoing intentional weight loss would experience changes in the levels of proinflammatory cytokines and several other biomarkers associated with the development of EC and other malignancies. METHODS Participants were selected on the basis of weight loss over a period of 12 months in two major behavioral weight loss trials ― SMART and PREFER ― conducted at the University of Pittsburgh. Serum samples were obtained at baseline, 6 and 12 months from 68 participants (baseline mean body mass index (BMI) was 33.62 ± 4.1 kg/m2). Twenty-six bead based xMAP immunoassays were used for this study, including cytokines, chemokines, and hormones. These biomarkers were chosen on the basis of their link to inflammation and cancer development in previous research. Repeated measures mixed models were used to evaluate the association between changes in biomarkers and BMI from baseline with and without adjustment for covariates, including age, gender, and race. RESULTS Participants lost an average of 16.83 kg from baseline to 12 months, with the largest change occurring in the first 6 months of the intervention. Both repeated measures ANOVA models (with and without covariates) demonstrated that among 26 biomarkers, changes in adiponectin, CRP, C-Peptide, IGFBP-1, insulin, leptin, PAI-1 (total), resistin, sE-selectin were significantly associated with BMI change. CONCLUSIONS This study contributes to an emerging literature beginning to explore biological mechanisms that may contribute to health benefits of even moderate weight loss. Results also emphasize the importance of further studies of biomarkers that showed significant changes after weight loss to determine the molecular pathways involved. Citation Format: Faina Y. Linkov, Marina Komaroff, Robert Edwards, Anna Lokshin, Mindi Styn, Dana Bovbjerg, Lora Burke. Associations between changes in circulating inflammatory biomarkers and reduced BMI achieved in SMART and PREFER behavioral weight loss interventions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2521. doi:10.1158/1538-7445.AM2013-2521