Pro-inflammatory cytokines and growth factors in human milk: an exploratory analysis of racial differences to inform breast cancer etiology
- 153 Downloads
Analysis of cytokines and growth factors in human milk offers a noninvasive approach for studying the microenvironment of the postpartum breast, which may better reflect tissue levels than testing blood samples. Given that Black women have a higher incidence of early-onset breast cancers than White women, we hypothesized that milk of the former contains higher levels of pro-inflammatory cytokines, adipokines, and growth factors.
Participants included 130 Black and 162 White women without a history of a breast biopsy who completed a health assessment questionnaire and donated milk for research. Concentrations of 15 analytes in milk were examined using two multiplex and 4 single-analyte electrochemiluminescent sandwich assays to measure pro-inflammatory cytokines, angiogenesis factors, and adipokines. Mixed-effects ordinal logistic regression was used to identify determinants of analyte levels and to compare results by race, with adjustment for confounders. Factor analysis was used to examine covariation among analytes.
Thirteen of 15 analytes were detected in ≥ 25% of the human milk specimens. In multivariable models, elevated BMI was significantly associated with increased concentrations of 5 cytokines: IL-1β, bFGF, FASL, EGF, and leptin (all p-trend < 0.05). Black women had significantly higher levels of leptin and IL-1β, controlling for BMI. Factor analysis of analyte levels identified two factors related to inflammation and growth factor pathways.
This exploratory study demonstrated the feasibility of measuring pro-inflammatory cytokines, adipokines, and angiogenesis factors in human milk, and revealed higher levels of some pro-inflammatory factors, as well as increased leptin levels, among Black as compared with White women.
KeywordsHuman milk Breast cancer risk Prevention Race
Funding was provided by National Cancer Institute (Bench to Bedside Award) to authors Mark E. Sherman, Kathleen F. Arcaro, and Gretchen L. Gierach.
Compliance with ethical standards
Conflict of interest
The authors state they have no conflict of interest.
- 5.DeSantis C, Ma J, Sauer AG et al. (2017) Breast Cancer Statistics, Racial Disparity in Mortality by State. CA Cancer J Clin. https://doi.org/10.3322/caac.2141
- 8.Hines EP, Rayner JL, Barbee R, Moreland RA, Valcour A, Schmid JE, Fenton SE (2007) Assays for endogenous components of human milk: comparison of fresh and frozen samples and corresponding analytes in serum. J Hum Lact 23(2):144–156. https://doi.org/10.1177/0890334407300334 CrossRefPubMedGoogle Scholar
- 11.Qin W, Zhang K, Kliethermes B et al. Differential expression of cancer associated proteins in breastmilk based on age at first full term pregnancy. BMC Cancer. 2012 Mar 21;12:100. https://doi.org/10.1186/1471-2407-12-100
- 14.Wong CM, Anderton DL, Smith-Schneider S, Wing MA, Griven MC, Arcaro K. Quantitative analysis of promoter methylation in exfoliated epithelial cells isolated from breast milk of healthy women. Epigenetics. 2010 Oct 1;5(7):645–655. https://doi.org/10.4161/epi.5.7.1296
- 19.Andreas NJ, Hyde MJ, Herbert BR et al (2016) Impact of maternal BMI and sampling strategy on the concentration of leptin, insulin, ghrelin and resistin in breast milk across a single feed: a longitudinal cohort study. BMJ Open 6(7):e010778. https://doi.org/10.1136/bmjopen-2015-010778 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Young B, Patinkin Z, Palmer C, de La Houssaye B, Barbour LA, Hernandez T, Friedman J, Krebs NF (2017) Human milk insulin is related to maternal plasma insulin and BMI - But other components of human milk do not differ by BMI. Eur J Clin Nutr 71(9):1094–1100. https://doi.org/10.1038/ejcn.2017.75 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Voronov E, Dotan S, Krelin Y, Song X, Elkabets M, Carmi Y, Rider P, Cohen I, Romzova M, Kaplanov I, Apte R (2013) Unique versus redundant functions of IL-1α and IL-1β in the tumor microenvironment. Front Immunol 4:177. https://doi.org/10.3389/fimmu.2013.00177 CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Collado MC, Santaella M, Mira-Pascual L, Martínez-Arias E, Khodayar-Pardo P, Ros G, Martínez-Costa C. Longitudinal study of cytokine expression, lipid profile and neuronal growth factors in human breast milk from term and preterm deliveries. Nutrients. 2015 Oct 19;7(10):8577–8591. https://doi.org/10.3390/nu7105415 CrossRefGoogle Scholar