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Blood Lead Levels and Mortality Risk in Cancer Patients: A Prospective Cohort Study with Mediation and Pan-Cancer Pathway Analysis
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DOI：10.1007/s12011-026-05270-8.png)
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Abstract
En 中文
Blood lead levels were associated with increased mortality in cancer patients, with mediation analyses suggesting a partial role of oxidative stress and inflammation, and heterogeneity across cancer types linked to Hallmark pathway activity. We analyzed 2,689 cancer patients from NHANES (1999–2016) using Cox regression, restricted cubic spline, and mediation analyses. Over 22,151.5 person-years, 983 deaths occurred. Compared with the lowest quartile, the highest blood lead quartile was associated with increased all-cause mortality (HR = 2.44; 95% CI: 1.79–3.34) and cancer mortality (HR = 2.34; 95% CI: 1.20–4.46). Lipid-adjusted inflammation indicators—including uric acid-to-high-density lipoprotein ratio (UHR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index (SIRI)—mediated 4.51–5.72% of the association, supporting partial mediation through oxidative stress and inflammation. The effect varied by cancer type and correlated with TCGA Hallmark pathway activities, including KRAS signaling (ρ = −0.95) and xenobiotic metabolism (ρ = 0.79), suggesting that molecular context modulates lead toxicity.
Keywords:
Blood lead
Hallmark pathway
NHANES
Mediation analysis
Mortality risk
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