title: Role of cytochrome P450 genes in breast cancer etiology and treatment: effects on estrogen biosynthesis, metabolism, and response to endocrine therapy.
abstract: OBJECTIVE
  The cytochrome P450 (CYP) genes are oxygenases involved in estrogen biosynthesis and metabolism, generation of DNA damaging procarcinogens, and response to anti-estrogen therapies. Since lifetime estrogen exposure is an established risk factor for breast cancer, determining the role of CYP genes in breast cancer etiology may provide critical information for understanding tumorigenesis and response to treatment.
  
  
  METHODS
  This review summarizes literature available in PubMed published between 1993 and 2013 that focuses on studies evaluating the effects of DNA variants in CYP genes on estrogen synthesis, metabolism, and generation of procarcinogens in addition to response to anti-estrogen therapies.
  
  
  RESULTS
  Evaluation of DNA variants in estrogen metabolism genes was largely inconclusive. Meta-analyses of data from CYP19A1 support an association between the number of (TTTA) n repeats in intron 4 and breast cancer risk, but the biological mechanism for this relationship is unknown. Associations between single nucleotide polymorphism in CYP1B1 and DNA damage caused by procarcinogenic estrogen metabolites were ambiguous. Variants in CYP2D6 are associated with altered metabolism tamoxifen; however, current data do not support widespread clinical testing. The effect of variants in CYP19A1 in response to aromatase inhibitors is also questionable.
  
  
  CONCLUSIONS
  Evaluation of DNA variants in CYP genes involved with estrogen metabolism or treatment response has been inconclusive, reflecting small samples sizes, tumor heterogeneity, and differences between populations. Better-powered studies that account for genetic backgrounds and tumor phenotypes are thus necessary.
authors.affiliation: Windber Research Institute, Windber, PA, 15963, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Blackburn
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Ellsworth
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shriver
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Ellsworth
mesh_terms: D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004249:DNA Damage; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007438:Introns; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D013629:Tamoxifen; D001141:Aromatase; C561410:CYP19A1 protein, human; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D019389:Cytochrome P-450 CYP2D6