Larsson SC, Kar S, Perry JRB, et al. - Findings indicate that endogenous 17β-estradiol (E2), the most potent estrogen, has a role in the development of estrogen receptor positive breast cancer and endometrioid endometrial cancer, but it was not strongly related to other cancers in women.

• From large-scale consortia, summary statistics genetic data for the link of the E2 variant with breast, endometrial, and ovarian cancer were collected, and among 198,825 women of European descent in UK Biobank, the links of the E2 variant with any and 20 site-specific cancers were estimated.

• Elevated risk of estrogen receptor positive breast cancer (OR 1.02), endometrial cancer overall (OR 1.09), and endometrial cancer of the endometrioid histology subtype (OR 1.10) was observed in relation to genetic predisposition to higher serum E2 levels.

• Suggestive links with breast cancer overall (OR 1.01), ovarian cancer of the endometrioid subtype (OR 1.05), and stomach cancer (OR 1.12) were found, but there was no significant relation to other cancers.