title: Role of CYP1A2 polymorphisms in breast cancer risk in women.
abstract: Cytochrome P4501A2 (CYP1A2) is a key enzyme in the etiology of breast cancer (BC). It is involved in breast carcinogen activation [aromatic (AAs) and heterocyclic amines (HAs), polycyclic aromatic hydrocarbons (PAHs)], in the production of beneficial oestrogen [2-hydroxyestrone (2-OHE1)] and in converting arachidonic acid (AAc) to epoxyeicosatrienoic acids (EETs), which have anti-inflammatory properties. Within a hospital-based case-control study, the effect of functional CYP1A2 variants [-3860G/A (rs2069514), -2467T/delT (rs3569413), -163C/A (rs762551)] and their interactions with environmental factors in BC risk was investigated. The study population included 125 BC cases and 43 non-cancer controls. Genotyping was performed in RT-PCR using Taqman assays. The gene-environment interaction was appraised using a case-only study design. We found that the -3860A variant, independently from environmental factors, as well as by interacting with fried foods (p=0.025) and indoor exposure to pollutants (p=0.050), reduced the risk of BC (p=0.025), whereas its interaction with coffee (p=0.045) increased the BC risk. This is the first study indicating that the -3860A variant, by decreasing CYP1A2 activity, modifies BC risk by interacting with environmental factors, thereby supporting the hypothesis that reduced CYP1A2 activity contributes to BC risk in different ways, for example, it may be protective by reducing the activation of pro-carcinogens such as AAs, HAs and PAHs, but would increase risk by reducing the beneficial formation of 2-OHE1 and EETs.
authors.affiliation: Metabolic Biophysics and Applied Pharmacology Laboratory, Department of Biophysics, University of Sousse, Sousse 4002, Tunisia.
authors.forename: Imene
authors.initials: I
authors.lastname: Ayari
authors.forename: Ugo
authors.initials: U
authors.lastname: Fedeli
authors.forename: Saad
authors.initials: S
authors.lastname: Saguem
authors.forename: Samir
authors.initials: S
authors.lastname: Hidar
authors.forename: Saida
authors.initials: S
authors.lastname: Khlifi
authors.forename: Sofia
authors.initials: S
authors.lastname: Pavanello
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D055815:Young Adult
chemical_list: D019388:Cytochrome P-450 CYP1A2