# Mendelian Randomization Analyses Reveal the Causal Effect of Cathepsin Z on the Risk of Different Subtypes of Thyroid Cancer

## TL;DR

This study finds that higher levels of cathepsin Z cause an increased risk of papillary thyroid cancer, using genetic data to establish a causal link.

## Contribution

The study is the first to use Mendelian randomization to establish a causal relationship between cathepsin Z and papillary thyroid cancer.

## Key findings

- Elevated cathepsin Z levels are causally linked to increased risk of papillary thyroid cancer.
- Papillary thyroid cancer does not appear to increase cathepsin Z levels.
- The findings suggest cathepsin Z could be a target for future cancer therapies.

## Abstract

Earlier research studies employing observational methods have suggested a possible relationship between the activity of cathepsin Z and thyroid cancer (TC). However, the causal relationship linking the cathepsin Z to TC has yet to be fully established, especially for different subtypes of TC.

The study employed accessible genomewide association study (GWAS) datasets to conduct bidirectional Mendelian randomization (MR) analyses. The primary approach for conducting MR analysis was the application of inverse variance weighting (IVW).

The MR analysis indicated that elevated cathepsin Z levels are positively linked to an elevated risk of papillary TC (PTC) development. In contrast, reverse MR indicated that PTC cannot contribute to increasing cathepsin Z levels.

Our MR analysis suggests a causal role of cathepsin Z in the development of PTC, offering valuable insights for future mechanistic studies and potential clinical applications targeting cathepsin-mediated pathways in cancer.