title: Age-associated gene expression in normal breast tissue mirrors qualitative age-at-incidence patterns for breast cancer.
abstract: BACKGROUND
  Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women's breast cancer may be more aggressive. Although, several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors is poorly understood. Characterizing age-related patterns of gene expression in normal breast tissues may provide insights on etiology of distinct breast cancer subtypes that arise from these tissues.
  
  
  METHODS
  To identify age-related changes in normal breast tissue, 96 tissue specimens from patients with reduction mammoplasty, ages 14 to 70 years, were assayed by gene expression microarray.
  
  
  RESULTS
  Significant associations between gene expression levels and age were identified for 802 probes (481 increased, 321 decreased with increasing age). Enriched functions included "aging of cells," "shape change," and "chemotaxis," and enriched pathways included Wnt/beta-catenin signaling, Ephrin receptor signaling, and JAK/Stat signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival.
  
  
  CONCLUSIONS
  The hazard rates of young-like tumors mirrored that of high-grade tumors in the Surveillance, Epidemiology, and End Results Program, providing a biologic link between normal aging and age-related tumor aggressiveness.
  
  
  CONCLUSIONS
  These data show that studies of normal tissue gene expression can yield important insights about the pathways and biologic pressures that are relevant during tumor etiology and progression.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Pirone
authors.forename: Monica
authors.initials: M
authors.lastname: D'Arcy
authors.forename: Delisha A
authors.initials: DA
authors.lastname: Stewart
authors.forename: William C
authors.initials: WC
authors.lastname: Hines
authors.forename: Melissa
authors.initials: M
authors.lastname: Johnson
authors.forename: Michael N
authors.initials: MN
authors.lastname: Gould
authors.forename: Paul
authors.initials: P
authors.lastname: Yaswen
authors.forename: D Joseph
authors.initials: DJ
authors.lastname: Jerry
authors.forename: Sallie
authors.initials: S
authors.lastname: Smith Schneider
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015994:Incidence; D016462:Mammaplasty; D008875:Middle Aged; D015398:Signal Transduction