In:
Breast Cancer Research, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2022-10-08)
Abstract:
Breast cancer (BC) has the highest cancer incidence and mortality in women worldwide. Observational epidemiological studies suggest a positive association between testosterone, estradiol, dehydroepiandrosterone sulphate (DHEAS) and other sex steroid hormones with postmenopausal BC. We used a two-sample Mendelian randomization analysis to investigate this association. Methods Genetic instruments for nine sex steroid hormones and sex hormone-binding globulin (SHBG) were obtained from genome-wide association studies (GWAS) of UK Biobank (total testosterone (TT) N : 230,454, bioavailable testosterone (BT) N : 188,507 and SHBG N : 189,473), The United Kingdom Household Longitudinal Study (DHEAS N : 9722), the LIFE-Adult and LIFE-Heart cohorts (estradiol N : 2607, androstenedione N : 711, aldosterone N : 685, progesterone N : 1259 and 17-hydroxyprogesterone N : 711) and the CORtisol NETwork (CORNET) consortium (cortisol N : 25,314). Outcome GWAS summary statistics were obtained from the Breast Cancer Association Consortium (BCAC) for overall BC risk ( N : 122,977 cases and 105,974 controls) and subtype-specific analyses. Results We found that a standard deviation (SD) increase in TT, BT and estradiol increased the risk of overall BC (OR 1.14, 95% CI 1.09–1.21, OR 1.19, 95% CI 1.07–1.33 and OR 1.03, 95% CI 1.01–1.06, respectively) and ER + BC (OR 1.19, 95% CI 1.12–1.27, OR 1.25, 95% CI 1.11–1.40 and OR 1.06, 95% CI 1.03–1.09, respectively). An SD increase in DHEAS also increased ER + BC risk (OR 1.09, 95% CI 1.03–1.16). Subtype-specific analyses showed similar associations with ER+ expressing subtypes: luminal A-like BC, luminal B-like BC and luminal B/HER2-negative-like BC. Conclusions TT, BT, DHEAS and estradiol increase the risk of ER+ type BCs similar to observational studies. Understanding the role of sex steroid hormones in BC risk, particularly subtype-specific risks, highlights the potential importance of attempts to modify and/or monitor hormone levels in order to prevent BC.
Type of Medium:
Online Resource
ISSN:
1465-542X
DOI:
10.1186/s13058-022-01553-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2041618-0
