Abstract
Background: The causal relationship between immune cells and renal cancer risk remains unclear, as observational studies are susceptible to confounding factors.To evaluate the causal relationship between immune cells and renal cancer risk using Mendelian randomization (MR), and validate findings through clinical cohort studies. Methods: MR analysis was conducted based on UKB-b-1316 dataset using three methods to assess causal relationships, with focus on secreting CD4 regulatory T cells. A cohort study of 527 renal cancer patients analyzed clinical characteristics and prognostic factors. Results: MR analysis revealed no significant causal relationship between immune cell levels and renal cancer risk overall, with most genetic instrumental variables' 95% confidence intervals crossing 1.0. Analysis of secreting CD4 regulatory T cells showed effect estimates of 0.006070 (P = 0.053) by inverse variance weighted method and 0.000695 (P = 0.024) by weighted median method, suggesting weak positive association with limited evidence. In the clinical cohort, clear cell RCC accounted for 71.7%, with median follow-up of 62.5 months and overall recurrence rate of 28.3%. Multifactorial analysis identified TNM stage ≥ T3 (HR = 3.25), Fuhrman nuclear grade ≥ 3 (HR = 2.13), histological subtype (HR = 1.87), microvascular invasion (HR = 1.78), and tumor size > 7 cm (HR = 1.56) as independent recurrence risk factors. Conclusions: MR analysis found no strong causal association between immune cells and renal cancer risk, with only CD4 regulatory T cells showing weak association.