Obesity as a modifiable risk factor in familial adenomatous polyposis.

94 Background: Familial Adenomatous Polyposis (FAP) is a rare, autosomal dominant cancer syndrome caused by mutations in the APC gene, characterized by the early development of hundreds to thousands of colorectal polyps and a near-certainty of colorectal cancer if untreated. While its genetic etiology is well defined, the effect of modifiable metabolic factors such as obesity, type 2 diabetes, and hyperlipidemia remains underexplored. Prior studies have demonstrated that obesity and type 2 diabetes significantly increase the risk of APC-driven gastrointestinal tumorigenesis, partly through mechanisms involving hyperinsulinemia, hyperlipidemia, and upregulation of Wnt/beta-catenin signaling and insulin-like growth factors (IGFs). Methods: We conducted a retrospective cohort study of 245 patients with Familial Adenomatous Polyposis (FAP) enrolled under an IRB-approved protocol PA12-0327 at MD Anderson Cancer Center from March 2013 to July 2025. Medical records were reviewed to gather demographic data and baseline clinical parameters, including body mass index (BMI), endoscopic findings, Spigelman stage, lipid profiles, blood glucose levels, and HbA1c. Descriptive statistics summarized baseline characteristics, and inferential analyses stratified by BMI were used to assess differences between groups. Results: Obese patients were more likely to present with Spigelman Stage II scores and a higher prevalence of desmoid tumors, whereas healthy-weight individuals were predominantly classified as Stage 0. However, no significant associations were found between obesity and cancer status (Previvor/Survivor/Active Cancer) or desmoid tumor behavior (Stable/Regression vs. Progression). Baseline analysis revealed no clear correlations between hyperglycemia, elevated HbA1c, or hyperlipidemia and disease severity, likely due to the limited availability of metabolic laboratory data at the initial visit. Conclusions: These findings suggest a potential association between obesity and increased duodenal polyp burden and desmoid tumor prevalence in FAP patients. While no link was observed between obesity and cancer or desmoid tumor progression status, the influence of modifiable metabolic factors warrants further investigation. The lack of complete baseline data limited a full assessment of glycemic and lipid-related variables. Longitudinal follow-up may offer deeper insights into how metabolic health influences FAP progression over time. These findings highlight the value of incorporating weight management, healthy diet, and physical activity into personalized care strategies for patients with hereditary cancer syndromes.