ArticleDiscover oncology2025
Genetic analysis the causal associations between metal elements and thyroid cancer: a bidirectional Mendelian randomization.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The Thyroid Under Pressure: Heavy Metals, Endocrine Disruptors and Translational Insights into Carcinogenesis and Thyroid Dysfunctions.International journal of molecular sciences · 2026Review
- Evaluating the causal role of LEPR signaling in 16 cancers: A drug-target Mendelian randomization study.Medicine · 2026Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundThyroid cancer is the most common endocrine malignancy worldwide, and recent studies suggest that environmental metal exposure may influence its development. However, existing evidence is mostly observational and lacks causal inference.
methodsWe performed a two-sample Mendelian randomization (MR) analysis to assess the causal relationships between 21 metal elements and thyroid cancer risk in East Asian populations. Genetic instruments were selected from a GWAS of 2488 individuals, and thyroid cancer summary statistics were obtained from 361 cases and 178,362 controls. The inverse-variance weighted (IVW) method was used as the primary analysis, with MR-Egger, weighted median, MR-PRESSO, and sensitivity analyses to assess robustness.
resultsIVW results identified a positive causal association between serum lead levels, OR = 1.608 (95% CI: 1.165-2.219; P = 0.004) and plasma manganese levels, OR = 1.332 (95% CI: 1.087-1.633; P = 0.006) with thyroid cancer. In contrast, plasma titanium levels were inversely associated with thyroid cancer risk, OR = 0.834 (95% CI: 0.697-0.997; P = 0.046). No evidence of reverse causation was found. Sensitivity analyses showed no significant heterogeneity or pleiotropy, supporting the robustness of the findings.
conclusionThis study provides the first genetic evidence for causal links between specific metal exposures and thyroid cancer. Elevated lead and manganese levels may increase cancer risk, while titanium may have a protective effect. These findings warrant further validation through mechanistic and longitudinal studies across diverse populations.
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