title: Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status.
abstract: BACKGROUND
  Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor-positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk.
  
  
  METHODS
  We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status.
  
  
  RESULTS
  We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors.
  
  
  CONCLUSIONS
  Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors.
authors.forename: Melissa
authors.initials: M
authors.lastname: Rotunno
authors.forename: Xuezheng
authors.initials: X
authors.lastname: Sun
authors.forename: Jonine
authors.initials: J
authors.lastname: Figueroa
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Paul
authors.initials: P
authors.lastname: Meltzer
authors.forename: Tyisha
authors.initials: T
authors.lastname: Williams
authors.forename: Sallie Smith
authors.initials: SS
authors.lastname: Schneider
authors.forename: D Joseph
authors.initials: DJ
authors.lastname: Jerry
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D010298:Parity / Q000235:genetics*; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D059467:Transcriptome; D055815:Young Adult
chemical_list: D011960:Receptors, Estrogen