The global obesity epidemic poses a major cancer risk, with over half of the world projected to be overweight or obese by 2035. Obesity increases the risk of at least 13 cancers, including breast and colorectal cancer, through metabolic, hormonal, and inflammatory mechanisms. The MeDOC consortium uses mouse models to study how obesity drives cancer initiation.
Obese adipose tissue acts as an active organ, secreting adipokines, cytokines, and hormones that promote inflammation, insulin resistance, and carcinogenesis. Postmenopausal estrogen elevation and gut microbiome alterations further enhance cancer risk. Proinflammatory macrophages can rise from 5% to 50% in fat tissue, creating a tumor-promoting environment. Mouse models mimic obesity genetically (leptin deficiency) or via high-fat diets, with MRI measuring fat distribution.
Using cancer initiation models like MPA/DMBA for breast cancer and AOM/DSS for colorectal cancer, researchers observe early lesions, tumor incidence, proliferation markers, and pathway activation (Wnt/β-catenin, PI3K/Akt). Preclinical studies confirm that obesity-driven inflammation and metabolic dysfunction accelerate early breast and colorectal cancer development.