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Blood Lead Levels and Mortality Risk in Cancer Patients: A Prospective Cohort Study with Mediation and Pan-Cancer
Jiukang Sun1, Wenyuan Gan2, Jing Zhou1
1Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Biological Trace Element Research
|August 10, 2026
Summary
High blood lead levels increase cancer patient mortality, with oxidative stress and inflammation playing a partial role. Lead toxicity varies by cancer type and is linked to specific molecular pathway activities.
Area of Science:
- Environmental Health
- Oncology
- Toxicology
Background:
- Elevated blood lead levels (BLLs) are a public health concern.
- Lead exposure is linked to various adverse health outcomes.
- The impact of BLLs on cancer patient mortality requires further investigation.
Purpose of the Study:
- To investigate the association between BLLs and mortality in cancer patients.
- To explore the mediating roles of oxidative stress and inflammation.
- To examine how cancer type and molecular pathway activity influence lead toxicity.
Main Methods:
- Analysis of 2,689 cancer patients from NHANES (1999-2016).
- Utilized Cox regression, restricted cubic spline, and mediation analyses.
- Examined associations with all-cause and cancer-specific mortality, and inflammation indicators (UHR, MLR, SIRI).
Main Results:
- The highest BLL quartile was associated with significantly increased all-cause (HR=2.44) and cancer mortality (HR=2.34).
- Inflammation indicators partially mediated the association between BLLs and mortality (4.51-5.72%).
- Lead's effect varied by cancer type and correlated with TCGA Hallmark pathways like KRAS signaling and xenobiotic metabolism.
Conclusions:
- Elevated BLLs are associated with increased mortality in cancer patients.
- Oxidative stress and inflammation partially mediate this association.
- Cancer-specific molecular context influences lead's toxicity, highlighting the need for personalized risk assessment.