Hypothyroidism has a protective causal association with hepatocellular carcinoma: A two-sample Mendelian...

Area of Science:

• Genetics
• Oncology
• Endocrinology

Background:

• Observational studies suggest a link between hypothyroidism and hepatocellular carcinoma (HCC) risk.
• Causality and the direction of this association remain unclear.

Purpose of the Study:

• To investigate the causal relationship between hypothyroidism and HCC risk using Mendelian randomization (MR).

Main Methods:

• Genome-wide association studies (GWAS) identified single-nucleotide polymorphisms (SNPs) for hypothyroidism.
• Summary-level data for HCC cases and controls were extracted from UK Biobank.
• Two-sample MR analysis with inverse-variance weighting (IVW) and sensitivity analyses were performed.

Main Results:

• Genetically predicted hypothyroidism showed an inverse association with HCC risk (OR = 0.997, P = 0.016).
• Sensitivity analyses confirmed the robustness of the findings, with no evidence of heterogeneity or pleiotropy.
• MR Steiger test indicated that hypothyroidism is causal for HCC, not vice versa.

Conclusions:

• Genetically determined hypothyroidism may reduce HCC risk, though the effect size is small.
• Further research is required to elucidate underlying mechanisms and explore clinical implications.
• Clinical trials are needed to determine if inducing hypothyroidism could benefit HCC patients.