title: CYP1B1 and hormone-induced cancer.
abstract: Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.
authors.affiliation: The Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, United Kingdom.
authors.forename: Ketan
authors.initials: K
authors.lastname: Gajjar
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Martin-Hirsch
authors.forename: Francis L
authors.initials: FL
authors.lastname: Martin
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000502:physiology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics; D051845:gamma-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D004967:Estrogens; D006728:Hormones; D051845:gamma-Synuclein; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1