Obesity and Cancer Risk: Epidemiological Evidence, Dose–Response Relationship, and Causal Inference

Abstract

Obesity has become a global public health challenge with important implications for the occurrence and development of many cancers. Epidemiological studies have shown that body mass index (BMI), waist circumference, waist-to-hip ratio, and visceral fat measured by imaging are all closely associated with an increased risk of cancer, involving sitespecific cancers such as colorectal, breast, endometrial, pancreatic, hepatocellular, renal, and esophageal adenocarcinoma. Prospective cohort studies and metaanalyses consistently confirmed a significant dose-response relationship, with an increase of approximately 18% in colorectal cancer, approximately 50% in endometrial cancer, and approximately 25% in kidney cancer for every 5 kg/m² increase in BMI. Mendelian randomized studies further support causal inference, and results from natural experiments and intervention studies such as bariatric surgery and long-term follow-up also show that obesityrelated cancer risk is reversible to some extent. Despite the limitations of measurement error, reverse causality and detection bias, the triangulation of cohort, meta, MR and intervention effectively enhanced the robustness of the research conclusions. Overall, there is a clear, stable, and cross-methodologically consistent dose-response relationship between obesity and cancer risk, providing a scientific basis for cancer prevention and control.