These results suggested that specific plasma proteins mediated the effects of obesity and smoking on kidney cancer, with nine proteins identified as shared mediators in both pathways: EFNA1, HAVCR2, IL10RB, IL18BP, MMP7, PGF, TGFBR2, TNFRSF1A, and TNFRSF1B (Fig. 4g). Here, TGFBR2 is linked to obesity due to melanocortin 4 receptor deficiency.