| Title: | Testosterone, sex hormone-binding globulin, insulin-like growth factor-1 and endometrial cancer risk: observational and Mendelian randomization analyses |
| Journal: | British Journal of Cancer |
| Published: | 6 Aug 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34363033/ |
| DOI: | https://doi.org/10.1038/s41416-021-01518-3 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548546 |
Publication 5802
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Abstract
BackgroundDysregulation of endocrine pathways related to steroid and growth hormones may modify endometrial cancer risk; however, prospective data on testosterone, sex hormone-binding globulin (SHBG) and insulin-like growth factor (IGF)−1 are limited. To elucidate the role of these hormones in endometrial cancer risk we conducted complementary observational and Mendelian randomization (MR) analyses.MethodsThe observational analyses included 159,702 women (80% postmenopausal) enrolled in the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. For MR analyses, genetic variants associated with hormone levels were identified and their association with endometrial cancer (12,906 cases/108,979 controls) was examined using two-sample MR.ResultsIn the observational analysis, higher circulating concentrations of total (HR per unit inverse normal scale = 1.38, 95% CI = 1.22-1.57) and free testosterone (HR per unit log scale = 2.07, 95% CI = 1.66-2.58) were associated with higher endometrial cancer risk. An inverse association was found for SHBG (HR per unit inverse normal scale = 0.76, 95% CI = 0.67-0.86). Results for testosterone and SHBG were supported by the MR analyses. No association was found between genetically predicted IGF-1 concentration and endometrial cancer risk.ConclusionsOur results support probable causal associations between circulating concentrations of testosterone and SHBG with endometrial cancer risk.</p>
6 Authors
- Amy Mullee
- Niki Dimou
- Naomi Allen
- Tracy O'Mara
- Marc J. Gunter
- Neil Murphy
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