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Background <p>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.</p> Methods <p>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.</p> Results <p>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<sup>–11</sup>). 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<sup>–7</sup>). Furthermore, the MR Steiger test demonstrated that LTL was causal for RCC, not vice-versa, with P &lt; 0.001.</p> Conclusion <p>Genetically determined longer LTL may increases RCC risk. Nevertheless, further research is essential to clarify the mechanisms driving this relationship.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年3月8日

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  • Xiao-bin Chen,
  • Li Wang,
  • Ping-yu Zhu

摘要

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 × 10–11). 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 × 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.