The effect of clinical medications for common diseases on cancer risk has attracted extensive attention. However, whether they have a causal relationship with lung cancer remains unclear. Genome-wide association study datasets on 23 drugs and lung cancer were extracted from publicly available databases. Mendelian randomization methods were utilized to assess the causal effects of the drugs on the risk of lung cancer. Sensitivity analyses were also conducted to evaluate the stability and reliability. Our results found that salicylic acid and derivatives (OR = 0.779; 95% CI, 0.676-0.898; P = 5 × 10, P-adjusted = 0.0125) significantly reduced lung cancer risk, while opioids (OR = 1.16; 95% CI, 1.065-1.263; P = 6 × 10, P-adjusted = 0.0148) significantly increased lung cancer risk. These findings remained robust after removing outliers. Suggestive evidence for a protective effect was also found for antithrombotic agents, antihypertensives, β-blockers, thyroid preparations, and anilines (all 0.0022 < P < 0.05). Notably, after outlier correction, the suggestive association for antithrombotic agents became statistically significant, while that for β-blockers disappeared, and the other suggestive associations persisted. Sensitivity analyses further confirmed the robustness of these findings. This study identified several clinical drugs that were causally associated with lung cancer, involving cardiovascular and endocrine system medications, anti-inflammatory/antipyretic analgesics, and centrally acting analgesics. It provides a theoretical reference for clinical medication guidance and understanding medication risks. -4 -4
