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Testosterone, sex hormone-binding globulin, insulin-like growth factor-1 and endometrial cancer risk: observational and Mendelian randomization analyses.
- Source :
-
British Journal of Cancer . Oct2021, Vol. 125 Issue 9, p1308-1317. 10p. - Publication Year :
- 2021
-
Abstract
- <bold>Background: </bold>Dysregulation 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.<bold>Methods: </bold>The 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.<bold>Results: </bold>In 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.<bold>Conclusions: </bold>Our results support probable causal associations between circulating concentrations of testosterone and SHBG with endometrial cancer risk. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 125
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 153221338
- Full Text :
- https://doi.org/10.1038/s41416-021-01518-3