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From Environmental Lead Exposure to Colorectal Cancer: Integrated Transcriptomic and Genetic Analyses Identify HMOX1
Ling Wang1, Yuning Qin2, Weizhen Wang1
1Chongqing College of Traditional Chinese Medicine, Chongqing, China.
Biological Trace Element Research
|August 6, 2026
Summary
Lead exposure
Area of Science:
- Environmental Health
- Genomics
- Cancer Research
Background:
- Colorectal cancer (CRC) is a significant cause of cancer mortality.
- The link between lead exposure and CRC mechanisms is not well understood.
Purpose of the Study:
- To identify candidate genes connecting lead exposure and CRC.
- To investigate the role of HMOX1 in the CRC microenvironment.
Main Methods:
- Integrated population data (NHANES), transcriptomics (RNA-seq), and genetic evidence.
- Utilized network toxicology and machine learning for gene prioritization.
- Performed single-cell RNA-seq, CellChat, and Mendelian randomization (MR).
Main Results:
- NHANES data showed a weakened association between blood lead and CRC after full adjustment.
- Prioritization identified HMOX1, IL1B, NLRP3, BCL2, MAPK3, and ALAD as candidate genes.
- HMOX1 was found in monocytes/macrophages, potentially involved in immune and oxidative stress signaling in CRC.
- Genetic evidence supported an association between HMOX1 expression and CRC risk.
- Molecular docking suggested plumbagin binds to HMOX1.
Conclusions:
- The crude association between blood lead and CRC is sensitive to adjustments.
- HMOX1 is a potential molecular link between lead exposure and colorectal cancer.
- Further experimental validation is needed to confirm HMOX1's role.
