Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study
Authors' conclusion
Our study does not provide strong evidence for a causal role of reproductive and hormonal factors in DTC risk, despite the observed sex disparity in incidence rates.
Study context
- Population
- European ancestry; Genome-wide association studies (GWAS) meta-analysis of six studies for differentiated thyroid carcinoma (DTC)7,705 cases · 963,612 controls
- Comparison
- Genetically predicted sex hormones, reproductive factors and gynecological conditions vs DTC risk
- Outcome
- DTC risk (OR, IVW)
Methodological detailsinverse-variance weighted method, sensitivity analyses, multivariable Mendelian randomization (MR) adjusting for body mass index (BMI) and TSH
- Inverse-variance weighted method
- Sensitivity analyses
- Multivariable MR adjusting for BMI and TSH
Main finding
As reported in the abstract
DTC risk
Sex hormone binding globulin (SHBG), OR (inverse-variance weighted (IVW))
1.13
p = 0.046
Bioavailable testosterone after BMI adjustment (multivariable MR (MVMR)), OR (IVW); positive but marginally significant
1.13
p = 0.07
Uterine fibroids in females <50 years, OR (IVW)
1.52
p = 0.017
Endometrial cancer, OR (IVW); genetic correlation r2 = 13% suggested potential pleiotropy
1.15
p = 9.0 × 10-3
Original publication
Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study. Thyroid. Published 26 March 2025. doi:10.
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