Association between leukocyte telomere length and renal cell carcinoma: insight from Mendelian randomization study

Background To investigate whether leukocyte telomere length (LTL) causally influences renal cell carcinoma (RCC) risk, this study applied Mendelian randomization (MR) analysis. Prior research examining LTL as a potential biomarker for RCC risk has yielded inconsistent findings. Methods We obtained summary-level LTL data from the UK Biobank genome-wide association study (n = 472,174) and gathered RCC data from both the FinnGen Consortium (n = 289,360) and the International Agency for Research on Cancer (IARC) (n = 13,230). To estimate odds ratios (OR) and 95% confidence intervals (CI), we primarily used the inverse-variance-weighted (IVW) method. We assessed potential heterogeneity and horizontal pleiotropy through Cochran's Q test, MR-PRESSO, and MR-Egger. We then integrated the estimates from these sources using random-effects meta-analysis techniques. Results Within the FinnGen Consortium, an increase in the genetically predicted LTL corresponds to an elevated risk of RCC development (IVW OR = 2.35; 95% CI 1.83-3.01; P = 2.07 x 10(-11)). This finding aligns with the outcomes observed in male patients within the IARC dataset (OR = 1.69; 95% CI 1.21-2.37; P = 0.002), although a consistent trend was not readily apparent among female patients. Sensitivity analyses validated the robustness of these findings. Upon pooling the results, a positive association between LTL and RCC risk was substantiated (OR = 1.96; 95% CI 1.52-2.52, p = 1.79 x 10(-7)). Furthermore, the MR Steiger test demonstrated that LTL was causal for RCC, not vice-versa, with P < 0.001. Conclusion Genetically determined longer LTL may increases RCC risk. Nevertheless, further research is essential to clarify the mechanisms driving this relationship.