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 × 10). 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 × 10). 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.