title: Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy.
abstract: BACKGROUND
  First full term pregnancy (FFTP) completed at a young age has been linked to low long term breast cancer risk, whereas late FFTP pregnancy age confers high long term risk, compared to nulliparity. Our hypothesis was that proteins linked to breast cancer would be differentially expressed in human milk collected at three time points during lactation based on age at FFTP.
  
  
  METHODS
  We analyzed breast milk from 72 lactating women. Samples were collected within 10 days of the onset of lactation (baseline-BL), two months after lactation started and during breast weaning (W). We measured 16 proteins (11 kallikreins (KLKs), basic fibroblast growth factor, YKL-40, neutrophil gelatinase-associated lipocalin and transforming growth factor (TGF) β-1 and -2) associated with breast cancer, most known to be secreted into milk.
  
  
  RESULTS
  During lactation there was a significant change in the expression of 14 proteins in women < 26 years old and 9 proteins in women > = 26 at FFTP. The most significant (p < .001) changes from BL to W in women divided by FFTP age (< 26 vs. > = 26) were in KLK3,6, 8, and TGFβ2 in women < 26; and KLK6, 8, and TGFβ2 in women > = 26. There was a significant increase (p = .022) in KLK8 expression from BL to W depending on FFTP age. Examination of DNA methylation in the promoter region of KLK6 revealed high levels of methylation that did not explain the observed changes in protein levels. On the other hand, KLK6 and TGFβ1 expression were significantly associated (r2 = .43, p = .0050).
  
  
  CONCLUSIONS
  The expression profile of milk proteins linked to breast cancer is influenced by age at FFTP. These proteins may play a role in future cancer risk.
authors.affiliation: Department of Surgery, University of North Dakota School of Medicine and Health Sciences, 501 N. Columbia Rd,, Grand Forks, ND 58202, USA.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qin
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Beth
authors.initials: B
authors.lastname: Kliethermes
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Ruhlen
authors.forename: Eva P
authors.initials: EP
authors.lastname: Browne
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Arcaro
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
mesh_terms: D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D020073:Gravidity; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D007774:Lactation / Q000235:genetics / Q000378:metabolism; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D008894:Milk Proteins; D009363:Neoplasm Proteins; D053773:Transforming Growth Factor beta1; C103551:KLK6 protein, human; D007610:Kallikreins