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

Area of Science:

• Endocrinology and Oncology
• Genetic Epidemiology

Background:

• Observational studies suggest a link between thyroid dysfunction and increased ovarian cancer (OC) risk.
• The causal relationship between thyroid dysfunction and OC remains uncertain.
• Mendelian randomization (MR) can help elucidate potential causal effects.

Purpose of the Study:

• To investigate the causal impact of thyroid dysfunction on ovarian cancer (OC) risk using a Mendelian randomization (MR) study.
• To determine if genetic predisposition to thyroid dysfunction influences OC risk.

Main Methods:

• Utilized genome-wide association study (GWAS) data for thyroid-related traits (TSH, FT4, hypothyroidism, hyperthyroidism) as exposures.
• Selected ovarian cancer (OC) data from a large cohort (N=199,741) as the outcome.
• Employed inverse variance-weighted (IVW) method and conducted sensitivity analyses to ensure result robustness.

Main Results:

• A genetic predisposition to hyperthyroidism was associated with a potential increase in ovarian cancer (OC) risk (OR=1.094, p=0.004).
• No significant causal effect was found for hypothyroidism, TSH, or FT4 on OC risk.
• Sensitivity analyses confirmed the reliability of the findings, showing no significant heterogeneity or pleiotropy.

Conclusions:

• This MR study provides evidence supporting a correlation between hyperthyroidism and increased ovarian cancer (OC) risk.
• Genetically predicted hyperthyroidism offers potential insights for early prevention and intervention strategies for OC.