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Steroids. 2015 Oct;102:1-6. doi: 10.1016/j.steroids.2015.06.014. Epub 2015 Jun 27.

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

Author information

1
Escuela de Nutrición, Universidad Autónoma del Estado de Morelos, Río Iztacihuatl s/n. Col. Vista Hermosa, C.P. 62350, Mexico.
2
Departamento de Biología Molecular, Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, C.P. 35010 Durango, Mexico.
3
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.
4
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.

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.

KEYWORDS:

Breast cancer; Catechol estrogens; Polymorphism

PMID:
26123186
DOI:
10.1016/j.steroids.2015.06.014
[Indexed for MEDLINE]

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