Differences in 4-hydroxyestradiol levels in leukocytes are related to CYP1A1(∗)2C, CYP1B1(∗)3 and COMT Val158Met allelic variants.

Abstract Exposure to estrogen and its metabolites, including catechol estrogens (CEs) and catechol estrogen quinones (CE-Qs) is closely related to breast cancer. Polymorphisms of the genes involved in the catechol estrogens metabolism pathway (CEMP) have been shown to affect the production of CEs and CE-Qs. In this study, we measured the induction of CYP1A1 , CYP1B1 , COMT , and GSTP1 by 17β-estradiol (17β-E 2 ) in leukocytes with CYP1A1 ∗ 2C , CYP1B1 ∗ 3 , COMT Val158Met and GSTP1 Ile105Val polymorphisms by semi quantitative RT-PCR and compared the values to those of leukocytes with wild type alleles; we also compared the differences in formation of 4- hydroxyestradiol (4-OHE 2 ) and DNA-adducts. The data show that in the leukocytes with mutant alleles treatment with 17β-E 2 up-regulates CYP1A1 and CYP1B1 and down-regulates COMT mRNA levels, resulting in major increments in 4-OHE 2 levels compared to leukocytes with wild-type alleles. Therefore, we propose induction levels of gene expression and intracellular 4-OHE 2 concentrations associated with allelic variants in response to exposure of 17β-E 2 as a noninvasive biomarker that can help determine the risk of developing non-hereditary breast cancer in women.