Phenotypic and genetically predicted leukocyte telomere length and prostate cancer risk: results from a large-scale longitudinal cohort study.

Background: Previous studies on the correlation between leukocyte telomere length (LTL) and prostate cancer (PCa) have shown inconsistent results. We aimed to clarify this association by leveraging a large-scale prospective design and Mendelian randomisation. Methods: We enrolled a total of 229 022 male individuals from the UK Biobank (UKB) to investigate the association between LTL and PCa risk. We employed both unadjusted and covariates-adjusted Cox proportional hazards regression models to assess this relationship. We defined the primary outcome as the diagnosis of incident PCa using in-patient data and the death registry of the UK Biobank cohort. To validate the reliability of the primary findings, we conducted secondary analyses, including Mendelian randomisation. Results: The primary analysis demonstrated that longer LTL was substantially associated with higher risk of PCa, with associations remaining robust after adjusting for potential covariates (hazard ratio (HR) = 1.444; 95% confidence interval (CI) = 1.247, 1.673, P < 0.001). We observed similar results when LTL was analysed as both a continuous and categorical variable, and the association was shown to be inversely U-shaped. We further validated the association at the genetic level using Mendelian randomisation across different PCa databases, with results consistent with our primary analysis. Conclusions: Our findings offer evidence that leukocyte telomere length is an important risk factor for PCa. Further studies are needed to elucidate the underlying mechanisms linking leukocyte telomere length to PCa risk.