Obesity and Cancer: Mechanisms, Epidemiological Evidence, and Potential Risk Reduction

Obesity promotes carcinogenesis through interlocking metabolic, inflammatory, immune, and hormonal pathways. We narratively synthesize recent meta-analyses and selected cohort studies that examine adiposity-principally body mass index (BMI) and waist circumference-in relation to cancer incidence. Across the 13 cancers designated by the U.S. National Cancer Institute as obesity-associated, risk elevations are generally consistent, though magnitudes vary by histology (e.g., esophageal adenocarcinoma vs. squamous cell carcinoma), anatomic subsite (gastric cardia vs. non-cardia), sex or menopausal status, and adiposity metric, with central adiposity often revealing additional risk beyond BMI. Evidence is mixed for several sites (e.g., pancreas and thyroid), and emerging but less established signals are noted for oral cavity, melanoma, bladder, non-Hodgkin lymphoma, and leukemia. We also review prevention data: observational studies and select trials suggest that intentional weight loss-via lifestyle interventions, pharmacotherapy (including glucagon-like peptide-1 receptor agonists), or bariatric surgery-can reduce overall or site-specific cancer incidence, although estimates are heterogeneous and causal certainty is limited. Taken together, biologic plausibility and convergent epidemiology support obesity as a modifiable cancer risk factor. Future studies are warranted using standardized exposure definitions, consistent stratification, and rigorous control of confounding to improve comparability. Adequately powered, long-term randomized or quasi-experimental studies may further refine effect sizes and inform precision prevention for obesity-related cancers.