The results indicated that MetS-Z mediated the association between CRP and overall cancer risk (ACME = 0.049; 95% CI = 0.031, 0.068, PM = 12.67%) and the risks of digestive system cancer (ACME = 0.038; 95% CI = 0.026, 0.050, PM = 10.16%) and obesity-related systemic tumours (ACME = 0.052; 95% CI = 0.036, 0.073, PM = 13.87%). This evidence concerns the gene CRP and obesity due to melanocortin 4 receptor deficiency.