Leukocyte telomere length and the risk of prostate cancer and benign prostatic hyperplasia: Insights from UK Biobank and Mendelian randomization study

Abstract Background Previous observational studies have been controversial regarding the association of leukocyte telomere length (LTL) with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Methods First, we conducted an observational study utilizing UK Biobank data. The correlation between LTL and the risk of PCa and BPH was evaluated via multivariate-adjusted logistic regression. Then, we conducted a two-sample Mendelian randomization (MR) to examine causal links between LTL (472,174 individuals) and PCa as well as BPH. To verify the reliability of primary analysis, we conducted a second analysis and sensitivity analyses. Results In the UK Biobank study, individuals in the longer quartiles of LTL were observed to have a higher risk of PCa (1.155-fold to 1.349-fold, all P<0.001) and BPH (1.119-fold to 1.212-fold, all P<0.001) compared to those in the lowest quartile in multivariate-adjusted logistic regression. We observed that genetically predicted longer LTL resulted in a 1.427-fold risk of PCa (odds ratio [OR]=1.427, 95% confidence interval [CI]=1.197–1.702, P<0.001) and 1.539-fold risk of BPH (OR=1.539, 95% CI=1.387–1.707, P<0.001) in primary analysis. In the second analysis, the results also indicated that longer LTL increased the genetic liability to both PCa (OR=1.338, 95% CI=1.189–1.507, P<0.001) and BPH (OR=1.006, 95% CI=1.003–1.008, P<0.001). Sensitivity analyses also supported the reliability of the results. Conclusions Our study provides convincing evidence supporting that longer LTL increases the risk of PCa and BPH in European individuals. Large-scale studies are needed to elucidate the potential mechanisms of LTL in PCa and BPH occurrence.