PMC

https://pmc.ncbi.nlm.nih.gov/articles/PMC11564068/ 

Highlights

•  Using data from a large prospective cohort study of 44,271 Japanese men, we decomposed the total causal effects of obesity on the risk of colorectal cancer (CRC) into three path-specific components: (1) direct effects; (2) indirect effects that are mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin, but by hyperinsulinemia and chronic inflammation, represented by circulating C-peptide and C-reactive protein, respectively.
• Our mediation analyses based on the multiple imputation indicated that there were indirect effects mediated by circulating leptin and adiponectin [risk ratio for body mass index (BMI) 25.0–27.4 kg/m2 was 1.29; 95% confidence interval, 0.98–1.69, and risk ratio for BMI ≥27.5 kg/m2 was 1.28; 95% confidence interval, 0.98–1.68], which may suggest a major role for these molecules in the pathway connecting obesity and CRC risk.
• Similar results were obtained using the inverse probability weighting method with design-based sampling probabilities (risk ratio for BMI 25.0–27.4 kg/m2 was 1.26; 95% confidence interval, 1.11–1.40, and risk ratio for BMI ≥27.5 kg/m2 was 1.49; 95% confidence interval, 1.06–1.89). 

Selected Result