Associations between Plasma Metal Concentrations and Mortality Risk in Non-Small-Cell Lung Cancer Patients: A Prospective Cohort Study.

Circulating metal concentrations have been implicated in lung cancer development and prognosis, but the impact of simultaneous exposure to multiple metals on mortality risk in non-small cell lung cancer (NSCLC) remains unclear. This study examined the associations of individual and joint plasma metal exposures with mortality risk in NSCLC patients. A total of 444 patients diagnosed with NSCLC between March 2015 and October 2019 were followed until August 2023. Thirteen plasma metals were quantified. Mortality risks were estimated using Cox proportional hazards regression. Bayesian Kernel Machine Regression (BKMR) analysis was applied to assess potential non-linear and interactive associations of metal mixtures, and posterior inclusion probabilities (PIPs) were used to evaluate the relative contributions of individual metal. During the follow-up, 301 patients (67.8%) died. After multivariable adjustments, higher plasma selenium (Se, Q4 vs. Q1: HR = 0.62; 95%CI = 0.44-0.87; P-trend = 0.008) and iron (Fe, HR = 0.56; 95% CI = 0.40-0.78; P-trend < 0.001) were associated with reduced mortality risk, while higher copper (Cu, HR = 2.37; 95%CI:1.66-3.38; P-trend < 0.001) was associated with increased risk. BKMR analyses supported these findings, with Cu showing the highest PIP, followed by Fe and Se. The overall exposure-response function suggested a non-significant trend toward reduced mortality risk with the joint exposure to all 13 metals. Both Cox regression and BKMR analyses indicated that higher plasma Se and Fe concentrations were associated with lower mortality risk in NSCLC patients, while higher Cu was associated with higher risk. Cu contributed the most to mortality risk. Larger, multi-center studies with longitudinal measurements and mechanistic investigations are warranted to validate these associations.