Affiliation:
1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , 75108 Uppsala , Sweden
Abstract
Abstract
Background
High levels of estrogen are associated with increased risk of breast and endometrial cancer and have been suggested to also play a role in the development of ovarian cancer. Cancerogenic effects of estradiol, the most prominent form of estrogen, have been highlighted as a side effect of estrogen-only menopausal hormone therapy. However, whether high levels of endogenous estrogens, produced within the body, promote cancer development, has not been fully established.
Objective
We aimed to examine causal effects of estradiol on breast, endometrial, and ovarian cancer.
Methods
Here we performed a two-sample Mendelian randomization (MR) to estimate the effect of endogenous estradiol on the risk of developing breast, endometrial, and ovarian cancer, using the UK Biobank as well as 3 independent cancer cohorts.
Results
Using 3 independent instrumental variables, we showed that higher estradiol levels significantly increase the risk for ovarian cancer (OR = 3.18 [95% CI, 1.47-6.87], P = 0.003). We also identified a nominally significant effect for ER-positive breast cancer (OR = 2.16 [95% CI, 1.09-4.26], P = 0.027). However, we could not establish a clear link to the risk of endometrial cancer (OR = 1.93 [95% CI, 0.77-4.80], P = 0.160).
Conclusion
Our results suggest that high estradiol levels promote the development of ovarian and ER-positive breast cancer.
Funder
Swedish Cancer Society
Swedish Research Council
Marcus Borgström Foundation
Hedströms Foundation
Åke Wiberg Foundation
Rudbergs Foundation
Vleugels Foundation
Subject
Endocrinology, Diabetes and Metabolism
Cited by
9 articles.
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