# Exploring the causal relationship between immune factors and chondrosarcoma: a Mendelian randomization study

## TL;DR

This study uses genetic data to explore how immune factors may cause chondrosarcoma, finding both positive and negative correlations.

## Contribution

The study provides novel causal insights into the relationship between immune factors and chondrosarcoma using Mendelian randomization.

## Key findings

- 12 immunocyte phenotypes were positively correlated with chondrosarcoma.
- 11 immunocyte phenotypes were negatively correlated with chondrosarcoma.
- Five inflammatory proteins showed positive associations with chondrosarcoma.

## Abstract

Previous studies have investigated the potential role of immune factors in chondrosarcoma (CHS). However, the causal relationship is unknown.

A two-sample Mendelian randomization (MR) was used to explore potential correlations between 731 immunocyte phenotypes, 91 inflammatory proteins, and CHS. The data were derived from published summary statistics of genome-wide association studies. Inverse-variance weighted was employed as the primary method. Furthermore, a range of analytical methods, including MR-Egger, weighted mode, and weighted median was used to enhance the robustness of the results. A two-step MR was used to assess the mediating effects of inflammatory proteins. Subsequently, sensitivity and MR Steiger directionality tests were performed.

MR analyses showed that 12 immunocyte phenotypes were positively correlated with CHS (P < 0.05, OR > 1), and 11 immunocyte phenotypes were negatively correlated with CHS (P < 0.05, OR < 1). Five inflammatory proteins were positively associated with CHS (P < 0.05, OR > 1). No heterogeneous or horizontal pleiotropy was found. The MR Steiger analysis found no statistically significant evidence of reverse causation. Mediation analysis did not identify any potential mediating effects.

Our study underscores the pivotal role of immune factors in CHS and offers insights that can inform future research.

The online version contains supplementary material available at 10.1007/s12672-025-02654-5.