Mendelian randomization analysis reveals causal roles of inflammatory cytokines in thyroid cancer pathogenesis

Thyroid cancer is a common endocrine malignancy associated with various inflammatory factors. This research aimed to explore the causal relationships between 41 inflammatory factors and the risk of thyroid cancer using Mendelian randomisation (MR) analysis. MR analysis was performed using genetic data from two publicly available European genome-wide association studies (GWAS). Instrumental variables were selected based on single-nucleotide polymorphisms significantly associated with cytokine levels. Causal relationships were assessed using the inverse variance weighted method, with sensitivity analyses to evaluate heterogeneity and pleiotropy. The results suggest that interleukin-1 receptor antagonist (IL-1RA) and β-nerve growth factor (B-NGF) are risk factors for thyroid cancer, while macrophage colony-stimulating factor (M-CSF) has a protective effect. IL-1RA, B-NGF, and M-CSF play a key role in regulating the tumour microenvironment compared with 38 other inflammatory factors that do not show a clear correlation. IL-1RA may promote cancer cell proliferation by activating pro-inflammatory signalling pathways, while B-NGF may enhance angiogenesis and immune escape, accelerating tumour progression. Conversely, M-CSF may reduce thyroid cancer risk by enhancing the anti-tumour immune response. Additionally, single-nucleotide polymorphism survival prognostic analysis showed that specific genetic variants associated with IL-1RA, B-NGF, and M-CSF may influence overall survival (OS) and cancer-specific survival (CSS) in patients with thyroid cancer, further supporting their potential value in thyroid cancer management. These findings suggest that IL-1RA and B-NGF could serve as novel biomarkers for early detection and disease monitoring of thyroid cancer, while M-CSF could be a potential therapeutic target, providing theoretical support for personalised intervention strategies. The results provide a new direction for precision medicine research in thyroid cancer.