Heavy metal exposure and cancer risk: Findings from a Mendelian randomization study

Epidemiological evidence has established associations between heavy metal exposure and increased risks of various cancers. However, causality remains difficult to establish in conventional observational studies due to residual confounding and reverse causation. Mendelian randomization (MR) could overcome these limitations by using genetic variants as instrumental variables to strengthen causal inference. This study employs a two-sample MR approach to investigate the potential causal effects of serum heavy metal concentrations on multiple cancer types.

Genetic instruments for heavy metal exposure were obtained from genome-wide association study (GWAS) data. The primary causal estimates were derived using the inverse variance weighted (IVW) method, with robustness assessed and pleiotropy addressed through supplementary analyses, including weighted median, MR-Egger regression, and MR-PRESSO. All analyses accounted for multiple testing via Bonferroni correction.

Mendelian randomization analysis revealed that genetically predicted serum nickel conferred an elevated risk of cervical cancer (OR = 1.473, 95 % CI: 1.102-1.969, P = 0.009), while serum manganese exhibited a protective effect against acute lymphoblastic leukemia (OR = 0.399, 95 % CI:0.173-0.922, P = 0.032). Additionally, serum lead was associated with an increased risk of biliary tract cancer (OR = 1.315, 95 % CI: 1.04-1.661, P = 0.022), and serum copper was causally linked to higher overall cancer incidence (OR = 1.052, 95 % CI: 1.004-1.102, P = 0.032).

This study provides solid evidence for causal effects of heavy metal exposure on cancer development. The findings compel further investigation into the biological mechanisms involved and highlight the urgency of developing targeted public health interventions to mitigate these risks.