Characteristics of cadmium’s impact on lung cancer burden and its toxicological mechanisms

Background: Environmental factors are modifiable factors. Understanding the distribution characteristics and changing trends of the global lung cancer burden caused by cadmium, and exploring the influencing mechanisms, are crucial for the implementation and intervention of precise public health policies. Methods: This study used the NHANES database to assess the association between cadmium and lung cancer prognosis via Kaplan-Meier analysis, Cox regression and RCS curves. The GBD database was used to analyze the global lung cancer burden attributable to cadmium (2021) and calculate EAPC values (1990–2021). The Nordpred modeling predicted future burdens up to 2050. Network toxicology and GEO database analysis identified key genes influencing prognosis post-cadmium exposure, with further evaluation of immune infiltration and single-cell sequencing. Results: Analysis using the NHANES database suggests an association between blood cadmium levels and lung cancer prognosis, supported by the Kaplan-Meier survival analysis (log-rank test P = 0.046). The Cox regression model, adjusted for covariates and based on median cadmium levels, is statistically significant(P = 0.023).Additionally, restricted cubic spline analysis shows a nonlinear relationship with all-cause mortality in lung cancer patients (P < 0.001). GBD analysis showed higher lung cancer burdens in men, older individuals, and high-middle SDI regions particularly China. Women and low-SDI regions had the highest EAPC values, with rising burdens expected. Network toxicology identified Bcl-2 as a potential target gene, with high expression in B cells, CD8 + T cells, and tumor cells. These cells showed enrichment in cell cycle and DNA repair pathways. Conclusion: Public health efforts should target high-burden populations. Monitoring and follow-up for both surgical and non-surgical lung cancer patients in high-cadmium areas or with elevated cadmium levels is crucial, along with enhanced education to mitigate exposure.Targeting BCL2 and related genes may mitigate cadmium-related lung cancer burden.