Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study

Area of Science:

• Endocrinology
• Oncology
• Genetics

Background:

• Gastric cancer is a leading global malignancy.
• Observational studies suggest a link between thyroid dysfunction and gastric cancer, but the relationship remains unclear.
• Mendelian randomization is employed to investigate causal links.

Purpose of the Study:

• To determine the causal relationship between thyroid dysfunction and gastric cancer.
• To provide insights for future clinical strategies and research into gastric cancer etiology.

Main Methods:

• Two-sample Mendelian randomization design using public GWAS data.
• Exposures: hyperthyroidism, hypothyroidism, free thyroxine (FT4), thyroid-stimulating hormone (TSH). Outcome: gastric cancer.
• Statistical analyses included Inverse-variance weighted (IVW), MR-Egger, and weighted median methods; sensitivity analyses were performed.

Main Results:

• A significant causal relationship was found between hypothyroidism and a reduced risk of gastric cancer (OR=0.936, P=0.006).
• Hypothyroidism acts as a protective factor against gastric cancer.
• No significant causal relationship was observed between hyperthyroidism, FT4, or TSH and gastric cancer.

Conclusions:

• Hypothyroidism is causally associated with a reduced risk of gastric cancer.
• The underlying mechanisms require further investigation through basic experiments.
• This finding offers a novel perspective on gastric cancer pathogenesis.