Bidirectional Mendelian randomization and mediation analysis of million-scale data reveal causal relationships between thyroid-related phenotypes, smoking, and lung cancer.

ABSTRACT: Emerging evidence highlights the role of thyroid hormones in cancer, although findings are controversial. Research on thyroid-related traits in lung carcinogenesis is limited. Using UK Biobank data, we performed bidirectional Mendelian randomization (MR) to assess causal associations between lung cancer risk and thyroid dysfunction (hypothyroidism and hyperthyroidism) or functional traits (free thyroxine [FT4] and normal-range thyroid-stimulating hormone [TSH]). Furthermore, in the smoking-behavior-stratified MR analysis, we evaluated the mediating effect of thyroid-related phenotypes on the association between smoking behaviors and lung cancer. We demonstrated significant associations between lung cancer risk and hypothyroidism (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.0

SUBMITTER: Wang X 

PROVIDER: S-EPMC12481675 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature