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. 2017 Aug 28;12(8):e0183579. doi: 10.1371/journal.pone.0183579

Table 3. Association between the protein levels of inflammatory markers in normal breast tissue and the predominant lobule typea.

Two-category quick scoreb Predominant lobule type
All women (n = 164) Premenopausal women (n = 82) Postmenopausal women (n = 82)
Pro-inflammatory markers N Crude Adjustedc N Crude Adjustedc N Crude Adjustedc
IL-6
 Low levelsd 64 1.00 1.00 24 1.00 1.00 40 1.00 1.00
 High levels 95 0.76 (0.52–1.11) 0.96 (0.68–1.34) 56 0.94 (0.37–2.42) 1.06 (0.43–2.60) 39 0.94 (0.66–1.35) 0.96 (0.68–1.35)
Pe 0.166 0.793 0.904 0.897 0.748 0.809
Pe,f 0.911 0.718 0.956
TNF-α
 Low levelsd 65 1.00 1.00 22 1.00 1.00 43 1.00 1.00
 High levels 95 0.62 (0.43–0.90) 0.82 (0.58–1.16) 58 0.38 (0.16–0.89) 0.43 (0.18–0.98) 37 1.03 (0.73–1.46) 1.05 (0.75–1.47)
Pe 0.014 0.266 0.055 0.072 0.876 0.767
Pe,f 0.467 0.118 0.630
CRP
 Low levelsd 76 1.00 1.00 23 1.00 1.00 53 1.00 1.00
 High levels 85 0.58 (0.40–0.85) 0.85 (0.59–1.23) 57 0.67 (0.28–1.64) 0.77 (0.32–1.86) 28 0.89 (0.61–1.30) 0.93 (0.64–1.35)
Pe 0.005 0.380 0.417 0.577 0.541 0.700
Pe,f 0.537 0.684 0.687
COX-2 (epithelial expression)
 Low levelsd 56 1.00 1.00 19 1.00 1.00 37 1.00 1.00
 High levels 103 0.50 (0.35–0.71) 0.65 (0.46–0.91) 61 0.24 (0.10–0.56) 0.26 (0.11–0.60) 42 0.85 (0.60–1.19) 0.89 (0.64–1.24)
Pe 0.0003 0.017 0.009 0.009 0.339 0.492
Pe,f 0.018 0.011 0.393
COX-2 (stromal expression)
 Low levelsd 18 1.00 1.00 5 1.00 1.00 13 1.00 1.00
 High levels 142 0.80 (0.49–1.33) 0.97 (0.63–1.48) 75 1.00 (0.16–6.11) 1.11 (0.20–6.27) 67 1.02 (0.64–1.63) 1.00 (0.66–1.53)
Pe 0.436 0.882 1.000 0.899 0.938 0.984
Pe,f 0.823 0.772 0.853
Leptin
 Low levelsd 59 1.00 1.00 22 1.00 1.00 37 1.00 1.00
 High levels 99 0.60 (0.41–0.86) 0.82 (0.58–1.16) 58 0.63 (0.26–1.53) 0.77 (0.32–1.84) 41 0.76 (0.54–1.09) 0.84 (0.59–1.18)
Pe 0.008 0.274 0.354 0.574 0.130 0.304
Pe,f 0.247 0.615 0.286
SAA1
 Low levelsd 38 1.00 1.00 15 1.00 1.00 23 1.00 1.00
 High levels 117 0.67 (0.45–0.98) 0.81 (0.57–1.17) 65 0.69 (0.26–1.85) 0.94 (0.37–2.37) 52 0.80 (0.56–1.15) 0.80 (0.56–1.15)
Pe 0.063 0.281 0.512 0.898 0.250 0.250
Pe,f 0.302 0.857 0.291
STAT3
 Low levelsd 22 1.00 1.00 8 1.00 1.00 14 1.00 1.00
 High levels 137 0.60 (0.41–0.87) 0.73 (0.53–1.00) 72 0.83 (0.23–3.00) 0.93 (0.29–2.99) 65 0.66 (0.49–0.90) 0.69 (0.52–0.93)
Pe 0.033 0.080 0.798 0.910 0.025 0.033
Pe,f 0.092 0.822 0.049
IL-8
 Low levelsd 10 1.00 1.00 3 1.00 1.00 7 1.00 1.00
 High levels 150 0.48 (0.33–0.70) 0.62 (0.42–0.91) 77 0.58 (0.11–3.08) 0.68 (0.16–2.98) 73 0.59 (0.49–0.71) 0.61 (0.47–0.80)
Pe 0.022 0.052 0.629 0.683 0.007 0.017
Pe,f 0.024 0.546 0.014
Anti-inflammatory markers
TGF-β
 Low levelsd 80 1.00 1.00 36 1.00 1.00 44 1.00 1.00
 High levels 81 0.99 (0.68–1.43) 1.14 (0.83–1.58) 44 1.80 (0.69–4.71) 1.84 (0.72–4.68) 37 0.93 (0.66–1.32) 0.99 (0.71–1.37)
Pe 0.948 0.417 0.207 0.180 0.701 0.943
Pe,f 0.362 0.214 0.996
IL-10
 Low levelsd 74 1.00 1.00 30 1.00 1.00 44 1.00 1.00
 High levels 77 0.57 (0.38–0.87) 0.72 (0.50–1.06) 48 0.63 (0.24–1.60) 0.66 (0.25–1.71) 29 0.76 (0.51–1.14) 0.78 (0.54–1.13)
Pe 0.007 0.087 0.348 0.403 0.164 0.180
Pe,f 0.118 0.403 0.185
Lactoferrin
 Low levelsd 51 1.00 1.00 20 1.00 1.00 31 1.00 1.00
 High levels 104 0.68 (0.47–0.99) 0.82 (0.59–1.15) 60 1.00 (0.36–2.75) 1.34 (0.47–3.80) 44 0.77 (0.54–1.09) 0.85 (0.62–1.17)
Pe 0.056 0.256 1.000 0.567 0.145 0.320
Pe,f 0.347 0.569 0.122

Abbreviations: IL-6, interleukin 6; TNF-α, tumor necrosis factor-α; CRP, C-reactive protein; COX-2, cyclooxygenase 2; SAA1, serum amyloid A1; STAT3, signal transducer and activator of transcription 3; IL-8, interleukin 8; TGF-β, transforming growth factor-β; IL-10, interleukin 10.

a Predominant lobule type was categorized as predominant type 1/no type 3 lobules vs. other lobule types.

b Quick score was dichotomized into low and high levels using the median of each marker as cut-off. Median of IL-6 = 2, TNF-α = 2, CRP = 2, COX-2 (epithelial expression) = 6, COX-2 (stromal expression) = 1, leptin = 6, SAA1 = 3, STAT3 = 3, IL-8 = 3, TGF-β = 1, IL-10 = 6, lactoferrin = 3.

c Adjusted for age at breast surgery.

d Referent category.

e Score test of heterogeneity.

f Adjusted for age at breast surgery and waist circumference. Analyses for all women were also adjusted for menopausal status.