- It is a minor pathway of estrogen metabolism.
- It may enhance cancer development.
- It may directly damage DNA by causing breaks in the molecular strands of DNA.
Human breast cancer tissue produces much higher levels of 4-OH-E1 than 2-OH-E1, while normal breast tissue produces approximately equal amounts of the two metabolites. Women taking hormone therapy with a polymorphism in CYP1B1 had twice the risk of developing breast cancer compared to other hormone therapy users.
Furthermore, the 4-Hydroxyestrones have the ability to convert to metabolites that react with DNA and cause mutations that can be carcinogenic. It is also present in greater quantities in patients deficient in methionine and folic acid. Women who have uterine fibroids also may have increased levels of 4-Hydroxyestrones.
- Spink BC, Fasco MJ, Gierthy JF, Spink DC. 12-O-tetradecanoylphorbol-13-acetate upregulates the Ah receptor and differentially alters CYP1B1 and CYP1A1 expression in MCF-7 breast cancer cells. J Cell Biochem. Sep 1 1998;70(3):289- 296.
- Hayes CL, Spink DC, Spink BC, Cao JQ, Walker NJ, Sutter TR. 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci USA. Sep 3 1996;93(18):9776-9781.
- Yang L, Gaikwad NW, Meza J, et al. Novel biomarkers for risk of prostate cancer: results from a case-control study. Prostate. Jan 1 2009;69(1):41-48.
- Castagnetta LA, Granata OM, Traina A, et al. Tissue content of hydroxyestrogens in relation to survival of breast cancer patients. Clin Cancer Res. Oct 2002;8(10):3146-3155.
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