# Mendelian randomization evidence based on European ancestry for the causal effects of leukocyte telomere length on prostate cancer

## TL;DR

This study finds that longer leukocyte telomere length increases prostate cancer risk and identifies several biological factors that may explain this link.

## Contribution

The study provides new causal evidence and identifies key mediators linking telomere length to prostate cancer.

## Key findings

- A 1-s.d. increase in leukocyte telomere length raises prostate cancer risk by 34%.
- Alzheimer’s disease, liver iron content, and other factors mediate the telomere-prostate cancer relationship.
- Adjusting for certain mediators reduces the observed effect of telomere length on prostate cancer.

## Abstract

Several lines of evidence suggest that leukocyte telomere length (LTL) can affect the development of prostate cancer (PC).

Here, we employed single nucleoside polymorphisms (SNPs) as instrumental variables (IVs) for LTL (n = 472,174) and conducted Mendelian randomization analysis to estimate their causal impact on PCs (79,148 patients/61,106 controls and 6311 patients/88,902 controls).

Every 1-s.d extension of LTL increased the risk of PCs by 34%. Additionally, the analysis of candidate mediators between LTL and PCs via two-step Mendelian randomization revealed that among the 23 candidates, Alzheimer’s disease, liver iron content, sex hormone binding global levels, naive CD4–CD8-T cell% T cell, and circulating leptin levels played substantial mediating roles. There is no robust evidence to support the reverse causal relationship between LTL and the selected mediators of PCs. Adjusting for the former four mediators, rather than adjusting for circulating leptin levels, decreased the impact of LTL on PCs.

This study provides potential intervention measures for preventing LTL-induced PCs.

The online version contains supplementary material available at 10.1186/s40246-024-00622-8.