The association between metabolic syndrome and lung cancer risk: a Mendelian randomization study

Metabolic syndrome (MetS) is closely linked to cancer development, with emerging evidence suggesting its association with pulmonary carcinoma. However, causal relationships remain unclear due to observational study limitations. Employing Mendelian randomization, we investigated the causal link between MetS and lung cancer (LC) susceptibility. The data utilized in this study were obtained from the publicly available genetic variation summary database. The causal relationship was assessed using the inverse variance weighting method (IVW), weighted median method, and MR-Egger regression. A sensitivity analysis was carried out to confirm the robustness of the findings. Furthermore, risk factor analyses were conducted to explore potential mediators. Utilizing various analyses, MetS demonstrated a significant positive association with LC (OR, 1.22; 95% CI, 1.09-1.37, p = 7.57 × 10^- 4), lung squamous cell carcinoma (LUSC) (OR, 1.47; 95%, 1.23-1.75, p = 2.22 × 10^- 5), and small cell lung cancer (SCLC) (OR, 1.76; 95% CI, 1.37-2.26, p = 8.20 × 10^- 6) but not lung adenocarcinoma (LUAD) (OR, 1.08; 95% CI, 0.94-1.24, p = 0.28). Risk factor analyses indicated that smoking, alcohol, body mass index, education, and type 2 diabetes might mediate the association. This study genetically validates and reinforces the evidence of MetS increasing the incidence of LC, including both LUSC) and SCLC, especially among individuals with abdominal obesity. It provides valuable insights for the development of lung cancer prevention strategies and directions for future research.