title: First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants.
abstract: OBJECTIVE
  Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype.
  
  
  METHODS
  The Marin Women's Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry.
  
  
  RESULTS
  A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = -0.31, 95 % CI -0.52, -0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95% CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants.
  
  
  CONCLUSIONS
  These findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes.
authors.affiliation: Marin County Department of Health and Human Services, 899 Northgate Drive, Suite 415, San Rafael, CA, 94903, USA, lprebil@cal.berkeley.edu.
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Prebil
authors.forename: Rochelle R
authors.initials: RR
authors.lastname: Ereman
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Powell
authors.forename: Farid
authors.initials: F
authors.lastname: Jamshidian
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
authors.forename: John A
authors.initials: JA
authors.lastname: Shepherd
authors.forename: Marc S
authors.initials: MS
authors.lastname: Hurlbert
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Benz
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001940:Breast / Q000473:pathology*; D000071060:Breast Density; D001943:Breast Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D046110:Hypertension, Pregnancy-Induced; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017526:Receptor, IGF Type 1