TY  - JOUR
AU  - Park, See Hyun
AU  - Sugier, Pierre-Emmanuel
AU  - Asgari, Yazdan
AU  - Karimi, Mojgan
AU  - Kaaks, Rudolf
AU  - Fortner, Renée Turzanski
AU  - Schulze, Matthias
AU  - Agnoli, Claudia
AU  - Pasanisi, Fabrizio
AU  - Sacerdote, Carlotta
AU  - Rodriguez-Barranco, Miguel
AU  - Aizpurua, Amaia
AU  - Cabrera Castro, Natalia
AU  - Guevara, Marcela
AU  - Tin Tin, Sandar
AU  - Weiderpass, Elisabete
AU  - de Vathaire, Florent
AU  - Lesueur, Fabienne
AU  - Guénel, Pascal
AU  - Mulot, Claire
AU  - Laurent-Puig, Pierre
AU  - Ostroumova, Evgenia
AU  - Boland-Auge, Anne
AU  - Deleuze, Jean-François
AU  - Thomsen, Hauke
AU  - Försti, Asta
AU  - Elisei, Rosella
AU  - Gemignani, Federica
AU  - Landi, Stefano
AU  - Rinaldi, Sabina
AU  - Elbaz, Alexis
AU  - Domenighetti, Cloé
AU  - Truong, Thérèse
TI  - Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study.
JO  - Thyroid
VL  - 35
IS  - 4
SN  - 1050-7256
CY  - Larchmont, NY
PB  - Liebert
M1  - DKFZ-2025-00651
SP  - 433-443
PY  - 2025
N1  - 2025 Apr;35(4):433-443
AB  - Background: Differentiated thyroid carcinoma (DTC) is occurring three times more frequently in females than in males. However, the underlying biological mechanisms driving this discrepancy remain poorly understood. To investigate the causal role of sex hormones and reproductive factors in the risk of DTC, we implemented a two-sample Mendelian randomization (MR) analysis. Methods: We utilized genome-wide association studies (GWAS) summary statistics to explore these associations. GWAS data on DTC were derived from a meta-analysis of six studies including 7705 cases and 963,612 controls of European ancestry. GWAS summary statistics on sex hormones, reproductive factors, and gynecological conditions were retrieved from publicly available sources. We used the inverse-variance weighted (IVW) method to estimate odds ratio (OR), with additional sensitivity analyses and conducted multivariable MR (MVMR) to account for potential confounding by body mass index (BMI) and thyrotropin (TSH). Results: We identified a positive association between sex hormone binding globulin (SHBG) and DTC (ORivw = 1.13, p = 0.046). After controlling for TSH and BMI in a MVMR analysis, the strength of this association remained similar but lost statistical significance. Bioavailable testosterone also showed a positive but marginally significant association with DTC after adjustment for BMI in the MVMR (ORivw = 1.13, p = 0.07). Putative causal association was observed with uterine fibroids in females under 50 years old (ORivw = 1.52, p = 0.017). Endometrial cancer was associated with DTC (ORivw = 1.15, p = 9.0 × 10-3); however, a genetic correlation of r2 = 13
KW  - Mendelian randomization (Other)
KW  - differentiated thyroid cancer (Other)
KW  - genetics epidemiology (Other)
KW  - hormones (Other)
KW  - reproductive factors (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40137860
DO  - DOI:10.1089/thy.2024.0548
UR  - https://inrepo02.dkfz.de/record/300165
ER  -