Abstract
BACKGROUND: The association between exposure to certain heavy metals and an increased risk of lung cancer has been confirmed, but the exact relationship remains uncertain. This research shed light on the association between blood metal elements and lung cancer, and examined their causal association through Mendelian randomization (MR). METHODS: This study retrospectively included 48,132 participants from 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression was employed for exploring the relationship between blood metal elements (cadmium, lead, mercury, selenium, manganese, cobalt, copper, iron, and zinc) and lung cancer. Additionally, MR analysis was carried out to investigate potential causal association between blood metal elements and the progression of lung cancer. RESULTS: A positive association was observed between cadmium and lung cancer, while a negative association was noted between iron and lung cancer when all confounders in the NHANES were fully taken into account. MR analysis further demonstrated that iron was negatively linked with lung adenocarcinoma (LUAD) in Europeans [odds ratio (OR)(ivw) =0.77, 95% confidence interval (CI): 0.65-0.92, P=0.004; OR(weighted median) =0.75, 95% CI: 0.61-0.92, P=0.006]. Sensitivity analyses confirmed the robustness and reliability of this finding (P>0.05). CONCLUSIONS: Iron is inversely related to the incidence of lung cancer, with MR analysis supporting its protective role in LUAD. These findings necessitate further validation in large-scale prospective cohort studies.