Investigating the Effect of Estradiol Levels on the Risk of Breast, Endometrial, and Ovarian Cancer.

Johansson Å, Schmitz D, Höglund J, Hadizadeh F, Karlsson T, Ek WE

J Endocr Soc 6 (8) bvac100 [2022-08-01; online 2022-06-29]

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. We aimed to examine causal effects of estradiol on breast, endometrial, and ovarian cancer. 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. 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). Our results suggest that high estradiol levels promote the development of ovarian and ER-positive breast cancer.

PubMed 35822202

DOI 10.1210/jendso/bvac100

Crossref 10.1210/jendso/bvac100

pmc: PMC9265484
pii: bvac100