title: Estrogen metabolism and breast cancer risk--a review.
abstract: The standard paradigm providing a general mechanistic explanation for the association of cumulative, excessive estrogen exposure and breast cancer risk is that estrogen and perhaps progesterone affect the rate of cell division; and thus manifest their effect on the risk of breast cancer by causing proliferation of breast epithelial cells. Proliferating cells are susceptible to genetic errors during DNA replication which, if uncorrected, can ultimately lead to a malignant phenotype. This standard paradigm has recently been expanded to encompass emerging research data supporting a complementary genotoxic pathway mediated by the generation and redox cycling of reactive oxygen species through the metabolic effects of estrogen metabolites such 4- and 16a-hydroxy catechols. This paradigm shift is necessitated by evidence of estrogen-induced carcinogenesis in several animal and human models following exposure to these estrogen metabolites. This review examines some of the available evidence relating these estrogen metabolites to animal and human breast carcinogenesis.
authors.affiliation: Department of Surgery, College of Medical Sciences, University of Benin, Benin City, Nigeria. michaelokobia@Yahoo.com
authors.forename: M N
authors.initials: MN
authors.lastname: Okobia
authors.forename: C H
authors.initials: CH
authors.lastname: Bunker
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008745:Methylation; D009249:NADP / Q000502:physiology; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D004967:Estrogens; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase