Abstract
OBJECTIVE: The objective is to investigate the causal link between inflammatory cytokines and lung cancer through the application of a two-sample bidirectional Mendelian randomization (MR) approach. METHOD: This study gathered data from genome-wide association studies (GWAS), focusing on 91 inflammatory cytokines associated with lung cancer. The investigation into the causal link between inflammatory cytokines and lung cancer was performed utilizing several methods, including the inverse variance weighted (IVW) approach, weighted median (WM) method, MR Egger regression, weighted mode, and simple mode. The IVW method served as the primary evaluative metric, while various sensitivity analyses were carried out to assess the heterogeneity and horizontal pleiotropy of the MR outcomes. RESULT: A total of 3 Inflammatory cytokines were identified as having a positive causal association with lung cancer. Among these, CCL25 (OR = 1.060, 95% CI 1.020-1.102) is a risk factor for lung cancer, increasing the risk of developing the disease; while GDNF (OR = 0.872, 95% CI 0.762-1.000) and IL-18 (OR = 0.852, 95% CI 0.781-0.930) are protective factors for lung cancer, reducing the risk of developing the disease. CONCLUSION: This research indicates a possible causal link between inflammatory cytokines and lung cancer, highlighting the involvement of several inflammatory cytokines in the disease's development. It offers fresh perspectives on how inflammatory cytokines mediate the pathogenesis of lung cancer, holding great importance for prevention, treatment, and symptom enhancement of the disease.