title: 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-E2) 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-OHE2) and DNA-adducts. The data show that in the leukocytes with mutant alleles treatment with 17β-E2 up-regulates CYP1A1 and CYP1B1 and down-regulates COMT mRNA levels, resulting in major increments in 4-OHE2 levels compared to leukocytes with wild-type alleles. Therefore, we propose induction levels of gene expression and intracellular 4-OHE2 concentrations associated with allelic variants in response to exposure of 17β-E2 as a noninvasive biomarker that can help determine the risk of developing non-hereditary breast cancer in women.
authors.affiliation: Escuela de Nutrición, Universidad Autónoma del Estado de Morelos, Río Iztacihuatl s/n. Col. Vista Hermosa, C.P. 62350, Mexico.
authors.forename: O C
authors.initials: OC
authors.lastname: Martínez-Ramírez
authors.affiliation: Departamento de Biología Molecular, Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, C.P. 35010 Durango, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Pérez-Morales
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510 México D.F., Mexico.
authors.forename: P
authors.initials: P
authors.lastname: Petrosyan
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510 México D.F., Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Castro-Hernández
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510 México D.F., Mexico.
authors.forename: M E
authors.initials: ME
authors.lastname: Gonsebatt
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510 México D.F., Mexico. Electronic address: juruli@unam.mx.
authors.forename: J
authors.initials: J
authors.lastname: Rubio
mesh_terms: D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000096:biosynthesis / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000096:biosynthesis / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D011110:Polymorphism, Genetic
chemical_list: D002393:Estrogens, Catechol; D004958:Estradiol; C014036:4-hydroxyestradiol; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Breast cancer; Catechol estrogens; Polymorphism