title: Association analysis between breast cancer genetic variants and mammographic density in a large population-based study (Determinants of Density in Mammographies in Spain) identifies susceptibility loci in TOX3 gene.
abstract: BACKGROUND
  Mammographic density (MD) is regarded as an intermediate phenotype in breast cancer development. This association study investigated the influence of 14 breast cancer susceptibility loci identified through previous genome-wide association studies on MD among the participants in the "Determinants of Density in Mammographies in Spain" (DDM-Spain) study.
  
  
  METHODS
  Our study covered a total of 3348 Caucasian women aged 45-68years, recruited from seven Spanish breast cancer screening centres having DNA available. Mammographic density was blindly assessed by a single reader using a semiquantitative scale. Ordinal logistic models, adjusted for age, body mass index and menopausal status, were used to estimate the association between each genotype and MD.
  
  
  RESULTS
  Evidence of association with MD was found for variant rs3803662 (TOX3) (Odds Ratio (OR)=1.13, 95% Confidence Interval (CI)=1.03-1.25), and marginal evidence of association for susceptibility loci rs3817198 (LSP1) (OR=1.09, 95% CI=1.00-1.20) and rs2981582 (FGFR2) (OR=0.92, 95% CI=0.84-1.01). Two other loci were associated with MD solely among pre-menopausal women, namely, rs4973768 (SLC4A7) (OR=0.83, 95% CI=0.70-1.00) and rs4415084 (MEPS30) (OR=1.22, 95% CI=1.00-1.49).
  
  
  CONCLUSIONS
  Our findings lend some support to the hypothesis which links these susceptibility loci to MD.
authors.affiliation: National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain. pfernandezn@isciii.es
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernandez-Navarro
authors.forename: Guillermo
authors.initials: G
authors.lastname: Pita
authors.forename: Carmen
authors.initials: C
authors.lastname: Santamariña
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Moreno
authors.forename: Carmen
authors.initials: C
authors.lastname: Vidal
authors.forename: Josefa
authors.initials: J
authors.lastname: Miranda-García
authors.forename: Nieves
authors.initials: N
authors.lastname: Ascunce
authors.forename: Francisco
authors.initials: F
authors.lastname: Casanova
authors.forename: Francisca
authors.initials: F
authors.lastname: Collado-García
authors.forename: Belen
authors.initials: B
authors.lastname: Herráez
authors.forename: Anna
authors.initials: A
authors.lastname: González-Neira
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
mesh_terms: D051017:Apoptosis Regulatory Proteins; D000071060:Breast Density; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006609:High Mobility Group Proteins; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D015534:Trans-Activators
chemical_list: D051017:Apoptosis Regulatory Proteins; D006609:High Mobility Group Proteins; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators