title: CYP2D6 gene variants and their association with breast cancer susceptibility.
abstract: BACKGROUND
  The gene encoding the phase I enzyme cytochrome P4502D6 (CYP2D6) has been previously investigated for its potential predictive role in the efficacy of breast cancer treatments such as tamoxifen, but its role in breast cancer susceptibility is unclear. This study aims to evaluate the association between germ line variations in CYP2D6 and breast cancer susceptibility.
  
  
  METHODS
  DNA samples from 13,472 cases and controls were genotyped for seven known functional variants [minor allele frequency (MAF) ≥ 0.01] and five single nucleotide polymorphisms (SNP) that tag common genetic variation (MAF > 0.05) in CYP2D6.
  
  
  RESULTS
  One relatively rare functional variant, CYP2D6*6, (MAF = 0.01) showed a modest increased association with breast cancer susceptibility (P(trend) = 0.02; OR = 1.32; 95% CI = 1.04-1.68). All other functional and tagSNPs showed no association with breast cancer susceptibility.
  
  
  CONCLUSIONS
  Common variants of CYP2D6 do not play a significant role in breast cancer susceptibility. However, this study raises questions regarding the role of rare variants, such as CYP2D6*6, in breast cancer susceptibility which merit further investigation.
  
  
  CONCLUSIONS
  This large case-control study, involving 13,472 women, found no evidence of any association between common CYP2D6 gene variants and breast cancer susceptibility. However, one relatively rare functional variant CYP2D6*6 showed a modest association with breast cancer susceptibility, indicating that the role of rare CYP2D6 variants in breast cancer risk is unclear and requires further investigation in an adequately powered study.
authors.affiliation: Department of Oncology and Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom. ja344@medschl.cam.ac.uk
authors.forename: Jean E
authors.initials: JE
authors.lastname: Abraham
authors.forename: Mel J
authors.initials: MJ
authors.lastname: Maranian
authors.forename: Kristy E
authors.initials: KE
authors.lastname: Driver
authors.forename: Radka
authors.initials: R
authors.lastname: Platte
authors.forename: Bolot
authors.initials: B
authors.lastname: Kalmyrzaev
authors.forename: Caroline
authors.initials: C
authors.lastname: Baynes
authors.forename: Craig
authors.initials: C
authors.lastname: Luccarini
authors.forename: Helena M
authors.initials: HM
authors.lastname: Earl
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D004273:DNA, Neoplasm; D019389:Cytochrome P-450 CYP2D6