Abstract
BACKGROUND: Currently there is no specific molecular biomarker for the diagnosis and treatment of renal cell carcinoma (RCC). Here we performed a gender-specific two-sample Mendelian randomization analysis to systematically assess the effects of circulating cytokines on RCC. METHODS: We have employed cis-quantitative trait loci as instrumental variables for the protein levels and expression of circulating cytokines. We estimated the causal effects of circulating cytokines on RCC risk in males and females with several Mendelian randomization methods. RESULTS: We observed a significant causal effect of Eotaxin on the increased risk of RCC in males (Odds ratio [OR] = 2.546, 95% confidence interval [CI] = 1.617-4.010, p value = 5.496 × 10-5), but not in females (OR = 1.352, 95% CI = 0.766-2.388, p value = 0.298). Besides, we also identified several cytokines as potentially associated with RCC in males including RANTES, MCP3, PDGFbb, TRAIL, and several other cytokines as potentially associated with RCC in females including sICAM and SCGFb. CONCLUSION: Our study highlighted that a higher level of circulating Eotaxin is causally associated with an increased risk of RCC in males but not in females. Further studies are needed to elucidate the exact mechanism and its potential application in the prognosis and treatment of RCC.