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Table 3 Multivariable-adjusted odds ratios (95% CI) for associations between tertiles of total erythrocyte fatty acid concentrations and subsequent breast cancer risk, stratified by tumor expression of immuno-inflammatory markers, Nurses’ Health Study II

From: Erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers and fatty acid synthase: a nested case-control study

  Tertile 1 Tertile 2 Tertile 3 Ptrend1 Tertile 1 Tertile 2 Tertile 3 Ptrend1 Phet2
  CD4low(n = 109)3 CD4high(n = 110)3  
Saturated fatty acids 1 (ref) 0.39 (0.20–0.76) 0.93 (0.51–1.71) 0.80 1 (ref) 0.50 (0.26–0.96) 0.98 (0.55–1.75) 0.77 0.94
Monounsaturated fatty acids 1 (ref) 0.93 (0.49–1.76) 0.84 (0.43–1.67) 0.63 1 (ref) 0.75 (0.40–1.40) 0.85 (0.45–1.60) 0.63 0.80
n-3 polyunsaturated fatty acids 1 (ref) 0.72 (0.37–1.38) 0.81 (0.43–1.53) 0.55 1 (ref) 0.77 (0.41–1.45) 0.69 (0.37–1.30) 0.26 0.61
n-6 polyunsaturated fatty acids 1 (ref) 0.57 (0.30–1.08) 0.93 (0.50–1.74) 0.80 1 (ref) 0.80 (0.43–1.49) 1.00 (0.55–1.82) 1.00 0.84
Trans fatty acids 1 (ref) 0.98 (0.51–1.88) 1.66 (0.85–3.23) 0.12 1 (ref) 1.50 (0.80–2.82) 1.52 (0.78–2.94) 0.25 0.75
  CD8low(n = 104)3 CD8high(n = 105)3  
Saturated fatty acids 1 (ref) 0.43 (0.23–0.83) 0.74 (0.40–1.34) 0.53 1 (ref) 0.44 (0.22–0.86) 1.12 (0.61–2.05) 0.42 0.34
Monounsaturated fatty acids 1 (ref) 0.88 (0.47–1.65) 0.81 (0.42–1.58) 0.55 1 (ref) 0.78 (0.41–1.48) 0.83 (0.43–1.61) 0.60 0.72
n-3 polyunsaturated fatty acids 1 (ref) 0.49 (0.25–0.95) 0.45 (0.23–0.87) 0.02 1 (ref) 1.14 (0.60–2.17) 1.19 (0.62–2.26) 0.62 0.04
n-6 polyunsaturated fatty acids 1 (ref) 1.19 (0.62–2.28) 1.63 (0.87–3.04) 0.12 1 (ref) 0.57 (0.31–1.08) 0.61 (0.32–1.14) 0.11 0.02
Trans fatty acids 1 (ref) 1.23 (0.64–2.35) 1.95 (1.00–3.82) 0.05 1 (ref) 1.37 (0.72–2.61) 1.56 (0.79–3.08) 0.21 0.51
  CD20low(n = 103)3 CD20high(n = 104)3  
Saturated fatty acids 1 (ref) 0.61 (0.32–1.16) 1.17 (0.64–2.16) 0.42 1 (ref) 0.25 (0.12–0.52) 0.79 (0.43–1.45) 0.83 0.72
Monounsaturated fatty acids 1 (ref) 1.05 (0.56–1.97) 0.75 (0.38–1.49) 0.39 1 (ref) 0.73 (0.39–1.39) 0.92 (0.47–1.77) 0.78 0.55
n-3 polyunsaturated fatty acids 1 (ref) 0.74 (0.38–1.43) 0.66 (0.34–1.29) 0.24 1 (ref) 0.75 (0.39–1.45) 0.88 (0.47–1.67) 0.74 0.76
n-6 polyunsaturated fatty acids 1 (ref) 0.71 (0.37–1.34) 0.78 (0.42–1.46) 0.44 1 (ref) 0.74 (0.38–1.43) 1.32 (0.72–2.44) 0.36 0.32
Trans fatty acids 1 (ref) 0.99 (0.52–1.91) 1.71 (0.87–3.37) 0.11 1 (ref) 1.73 (0.89–3.34) 1.77 (0.89–3.53) 0.13 0.73
  CD163low(n = 110)3 CD163high(n = 111)3  
Saturated fatty acids 1 (ref) 0.35 (0.18–0.69) 1.04 (0.58–1.88) 0.55 1 (ref) 0.57 (0.31–1.06) 0.87 (0.49–1.56) 0.85 0.66
Monounsaturated fatty acids 1 (ref) 0.86 (0.46–1.61) 0.85 (0.44–1.67) 0.65 1 (ref) 0.76 (0.41–1.40) 0.82 (0.44–1.53) 0.54 0.81
n-3 polyunsaturated fatty acids 1 (ref) 0.82 (0.43–1.58) 1.02 (0.54–1.93) 0.88 1 (ref) 0.70 (0.37–1.30) 0.58 (0.31–1.08) 0.09 0.13
n-6 polyunsaturated fatty acids 1 (ref) 0.91 (0.49–1.70) 0.98 (0.53–1.81) 0.94 1 (ref) 0.54 (0.29–1.02) 0.94 (0.53–1.68) 0.79 0.76
Trans fatty acids 1 (ref) 1.19 (0.63–2.23) 1.51 (0.78–2.95) 0.22 1 (ref) 1.28 (0.68–2.41) 1.92 (1.01–3.67) 0.05 0.64
  Low CD4/CD8 ratio (n = 100)3 High CD4/CD8 ratio (n = 100)3  
Saturated fatty acids 1 (ref) 0.29 (0.14–0.59) 0.90 (0.49–1.64) 0.85 1 (ref) 0.66 (0.35–1.26) 1.00 (0.54–1.86) 0.83 0.88
Monounsaturated fatty acids 1 (ref) 0.91 (0.47–1.77) 1.22 (0.62–2.40) 0.52 1 (ref) 0.67 (0.36–1.26) 0.48 (0.24–0.96) 0.04 0.008
n-3 polyunsaturated fatty acids 1 (ref) 0.88 (0.46–1.71) 0.93 (0.48–1.80) 0.86 1 (ref) 0.69 (0.36–1.32) 0.58 (0.30–1.12) 0.11 0.20
n-6 polyunsaturated fatty acids 1 (ref) 0.62 (0.33–1.16) 0.75 (0.40–1.43) 0.36 1 (ref) 0.97 (0.50–1.88) 1.30 (0.69–2.46) 0.40 0.11
Trans fatty acids 1 (ref) 1.54 (0.79–3.02) 1.77 (0.87–3.59) 0.13 1 (ref) 1.25 (0.65–2.39) 1.76 (0.90–3.44) 0.10 0.62
  COX-2low(n = 103)3 COX-2high(n = 104)3  
Saturated fatty acids 1 (ref) 0.47 (0.24–0.89) 0.90 (0.50–1.65) 0.99 1 (ref) 0.38 (0.19–0.75) 1.10 (0.61–1.98) 0.39 0.34
Monounsaturated fatty acids 1 (ref) 0.84 (0.45–1.58) 0.86 (0.45–1.65) 0.65 1 (ref) 0.81 (0.44–1.51) 0.72 (0.37–1.42) 0.35 0.73
n-3 polyunsaturated fatty acids 1 (ref) 0.46 (0.23–0.89) 0.60 (0.31–1.13) 0.14 1 (ref) 1.08 (0.58–2.01) 0.82 (0.43–1.56) 0.53 0.76
n-6 polyunsaturated fatty acids 1 (ref) 0.94 (0.49–1.81) 1.36 (0.74–2.52) 0.31 1 (ref) 0.59 (0.32–1.09) 0.69 (0.37–1.29) 0.23 0.06
Trans fatty acids 1 (ref) 1.32 (0.71–2.47) 1.65 (0.83–3.26) 0.15 1 (ref) 1.39 (0.71–2.72) 2.08 (1.06–4.07) 0.03 0.24
  1. Cases and controls were matched on case diagnosis date, age at blood collection (± 2 years), menopausal status at blood collection and in the questionnaire cycle before cancer diagnosis/control index date (premenopausal, postmenopausal, unknown), self-reported race/ethnicity (white, non-white), fasting status at blood collection (< 2, 2–4, 5–7, 8–11, ≥ 12 h since last meal), and month (± 1 month) and time of day (± 2 h) of blood collection. Women who were premenopausal at blood collection and provided samples timed in the menstrual cycle were further matched on luteal day (± 1 day), and postmenopausal women were further matched on menopausal hormone therapy use at blood collection (yes, no). Tertiles of fatty acids were defined based on tertile cutpoints among controls (Additional file 1: Supplemental Methods). Multivariable unconditional logistic regression models were adjusted for matching factors and the following potential confounders: age at menarche (< 12, 12, 13, ≥ 14 years), parity/age at first birth (nulliparous, 1–2 births/age first birth< 25, 1–2 births/age first birth ≥ 25, ≥ 3 births/age first birth < 25, ≥ 3 births/age first birth ≥ 25), history of breastfeeding (yes, no), family history of breast cancer (yes, no), history of biopsy-confirmed benign breast disease (yes, no), BMI at age 18 (< 21, 21 to < 23, ≥ 23 kg/m2), weight change between age 18 and blood collection (continuous, kg), average alcohol consumption from 1991 and 1995 questionnaires (< 5, ≥ 5 g/day), and average physical activity from 1989, 1991, and 1997 questionnaires (< 3, 3 to < 9, 9 to < 18, 18 to < 27, ≥ 27 Metabolic Equivalent of Task [MET]-hours/week)
  2. Abbreviations: CI confidence interval, COX-2 cyclooxygenase-2
  3. 1P trend calculated by modeling the median of each tertile among controls as a continuous variable, testing for linearity using the Wald test
  4. 2P heterogeneity calculated using unconditional nominal polytomous logistic regression adjusted for matching factors and confounders, testing for heterogeneity using the Wald test with the model-based variance-covariance matrix estimate and allowing the effects of covariates to vary by tumor subtype
  5. 3Low vs. high tumor expression subtype was based on the median percent positivity in stromal cells for CD4 (4.2%), CD8 (5.5%), CD20 (0.6%), CD163 (13.2%), and CD4/CD8 ratio (0.7) and on the median percent positivity in epithelial cells for COX-2 (26.9%). COX-2 was defined as the percentage of epithelial area staining positive for at least one of the two antibodies (Cayman Chemical or Thermo Fisher Scientific)