Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy

First full term pregnancy (FFTP) completed at a young age hasbeen linked to low long term breast cancer risk, whereas late FFTP pregnancyage confers high long term risk, compared to nulliparity. Our hypothesis wasthat proteins linked to breast cancer would be differentially expressed in humanmilk collected at three time points during lactation based on age at FFTP.Methods: We analyzed breast milk from 72 lactating women. Samples werecollected within 10 days of the onset of lactation (baseline-BL), two monthsafter lactation started and during breast weaning (W). We measured 16 proteins(11 kallikreins (KLKs), basic fibroblast growth factor, YKL-40, neutrophilgelatinase-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 14proteins in women < 26 years old and 9 proteins in women > = 26 at FFTP. Themost significant (p < .001) changes from BL to W in women divided by FFTPage (< 26 vs. > = 26) were in KLK3,6, 8, and TGFβ2 in women < 26; andKLK6, 8, and TGFβ2 in women > = 26. There was a significant increase (p =.022) in KLK8 expression from BL to W depending on FFTP age. Examinationof DNA methylation in the promoter region of KLK6 revealed high levels ofmethylation that did not explain the observed changes in protein levels. On theother hand, KLK6 and TGFβ1 expression were significantly associated (r2 =.43, p = .0050).Conclusions: The expression profile of milk proteins linked to breast cancer isinfluenced by age at FFTP. These proteins may play a role in future cancer risk.

Keywords:

Lactation , Breast cancer risk , First full term pregnancy , Milk proteins Funded in part by Avon Foundation for Wom