Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study.

Area of Science:

• Endocrinology
• Oncology
• Genetics

Background:

• Differentiated thyroid carcinoma (DTC) affects females three times more often than males.
• The biological basis for this sex disparity in DTC incidence is not well understood.
• Investigating the influence of sex hormones and reproductive factors is crucial.

Purpose of the Study:

• To explore the potential causal relationships between sex hormones, reproductive factors, and the risk of differentiated thyroid carcinoma (DTC).
• To utilize Mendelian randomization to assess these associations, accounting for potential confounders.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was performed.
• Genome-wide association studies (GWAS) summary statistics for DTC, sex hormones, and reproductive factors were used.
• Inverse-variance weighted (IVW) and multivariable MR (MVMR) methods were employed, adjusting for BMI and TSH.

Main Results:

• A positive association was observed between sex hormone binding globulin (SHBG) and DTC risk, which lost significance after adjusting for TSH and BMI.
• Bioavailable testosterone showed a marginally significant positive association with DTC risk after BMI adjustment.
• A putative causal association was found between uterine fibroids and DTC in premenopausal females.
• Endometrial cancer was associated with DTC, though potential pleiotropy was noted.

Conclusions:

• The study found limited strong evidence for a causal role of investigated reproductive and hormonal factors in DTC risk.
• Observed associations with SHBG, bioavailable testosterone, uterine fibroids, and endometrial cancer suggest potential risk factors requiring further investigation.
• The underlying reasons for the higher incidence of DTC in females remain largely unexplained by these factors.