Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and
Hong Tang1, Na Tang2, Yueling Liao3
1Department of Spine surgery, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, P. R. China.
Discover Oncology
|July 31, 2025
Summary
This study found that certain inflammatory proteins (GCST90274776, GCST90274822, GCST90274847) may increase osteosarcoma risk. Conversely, GCST90274844 appears to offer a protective effect against osteosarcoma.
Area of Science:
- Genetics and Molecular Biology
- Oncology
- Immunology
Background:
- Osteosarcoma is a primary bone cancer with complex etiology.
- Circulating inflammatory proteins are implicated in various cancers, but their causal role in osteosarcoma remains unclear.
Purpose of the Study:
- To investigate the potential causal links between 91 circulating inflammatory proteins and osteosarcoma risk.
- To leverage the two-sample Mendelian randomization (MR) method for robust causal inference.
Main Methods:
- Utilized genome-wide association study (GWAS) data for exposure (inflammatory proteins) and outcome (osteosarcoma).
- Performed two-sample Mendelian randomization analysis with inverse-variance weighted (IVW) as the primary method.
- Employed MR-Egger, weighted median, and other methods for sensitivity analyses and result validation.
Main Results:
- Identified positive causal relationships between GCST90274776, GCST90274822, and GCST90274847 and osteosarcoma.
- Observed a negative causal relationship between GCST90274844 and osteosarcoma.
- Sensitivity and supplementary analyses confirmed the reliability and consistency of these findings.
Conclusions:
- Suggests that GCST90274776, GCST90274822, and GCST90274847 may act as risk factors for osteosarcoma development.
- Indicates that GCST90274844 may possess a protective effect against osteosarcoma.
- Highlights the potential of specific inflammatory proteins as therapeutic targets or biomarkers for osteosarcoma.
