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Table 2 Stratified analysis of average methylation levels and breast cancer risk by several characteristics

From: Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies

Characteristics OR* 95% CI* P value* P hete I2 (95% uncer. int.) OR§ 95% CI§ P value§ P hete I2 (95% uncer. int.)
Age at blood draw (years)
 < 50 1.11 (0.82,1.50) 0.49 0.17 0.0 (0.0, 89.5) 1.04 (0.72, 1.51) 0.82 0.57 0.0 (−)
 ≥ 50 0.89 (0.81, 0.99) 0.03   0.0 (0.0, 75.8) 0.93 (0.84, 1.04) 0.22   0.0 (0.0, 0.0)
ER status
 ER+ 0.92 (0.83, 1.02) 0.10 0.88 0.0 (0.0, 66.1) 0.93 (0.83, 1.05) 0.25 0.46 0.07 (0.0, 0.0)
 ER− 0.93 (0.76, 1.15) 0.51   40.5 (0.0, 79.9) 1.04 (0.81, 1.34) 0.77   0.0 (0.0, 83.8)
Stage
 Early 0.94 (0.84, 1.06) 0.34 0.20 0.0 (0.0, 76.0) 0.90 (0.79, 1.03) 0.13 0.68 0.0 (0.0, 72.4)
 Late 0.83 (0.71, 0.97) 0.02   9.7 (0.0, 86.2) 0.95 (0.79, 1.13) 0.55   0.0 (0.0, 80.5)
Time since diagnosis
 < 2 years 0.96 (0.75, 1.24) 0.78 0.68 11.4 (0.0, 86.4) 0.99 (0.72, 1.37) 0.96 0.80 0.0 (0.0, 77.4)
 ≥ 2 years 0.91 (0.83, 1.00) 0.06   24.9 (0.0, 88.3) 0.95 (0.85, 1.06) 0.34   0.0 (0.0, 26.5)
Time since diagnosis
 < 5 years 0.93 (0.78, 1.10) 0.39 0.98 71.4 (18.6, 90.0) 0.93 (0.75, 1.14) 0.47 0.99 19.4 (0.0, 87.7)
 ≥ 5 and ≤ 10 years 0.92 (0.81, 1.04) 0.20   0.0 (0.0, 71.3) 0.94 (0.81, 1.08) 0.37   0.0 (0.0, 74.0)
 > 10 years 0.94 (0.80, 1.11) 0.46   0.0 (0.0, 56.2) 0.93 (0.77, 1.12) 0.46   0.0 (0.0, 70.6)
CpG region
 CpG island 0.93 (0.85, 1.02) 0.13 0.98 0.0 (0.0, 79.6) 0.98 (0.87, 1.10) 0.74 0.95 0.0 (0.0, 71.1)
 CpG shore 0.92 (0.84, 1.00) 0.06   0.0 (0.0, 23.0) 0.94 (0.84, 1.04) 0.23   0.0 (0.0, 0.0)
 CpG shelf 0.94 (0.86, 1.03) 0.20   58.7 (0.0, 86.3) 0.96 (0.86, 1.06) 0.42   0.0 (0.0, 27.1)
 Open sea 0.94 (0.86, 1.03) 0.18   62.3 (0.0, 87.3) 0.95 (0.85, 1.05) 0.31   0.0 (0.0, 60.9)
Regulatory region
 Promoter 0.90 (0.82, 0.99) 0.03 0.95 0.0 (0.0, 65.5) 0.93 (0.83, 1.04) 0.20 0.96 0.0 (0.0, 64.0)
 Gene body 0.93 (0.85, 1.02) 0.14   48.1 (0.0, 82.8) 0.96 (0.87, 1.07) 0.46   0.0 (0.0, 62.3)
 3′UTR 0.93 (0.85, 1.02) 0.12   59.8 (0.0, 86.6) 0.96 (0.87, 1.07) 0.50   0.0 (0.0, 50.8)
 Intergenic 0.92 (0.84, 1.01) 0.07   53.7 (0.0, 84.7) 0.94 (0.85, 1.04) 0.27   0.0 (0.0, 64.4)
  1. The I2 statistic estimates (in percent) how much of the total variability in the effect size estimates (which is composed of heterogeneity and sampling variability) can be attributed to heterogeneity among the true effects. I2 varies from 0 to 100%
  2. P heterogeneity: Tests whether the variability in the observed effect sizes across strata is larger than would be expected based on sampling variability alone
  3. Stage: a cancer was considered an early stage if it was classified as localized (EPIC-Italy, EPIC-IARC) or stage I (MCCS, PLCO). A cancer was considered late-stage if it was classified as regional or metastatic (EPIC-Italy, EPIC-IARC) or stages II, III, or IV (MCCS, PLCO)
  4. CpG region: shore 0–2 kb from CpG island, shelf = 2–4 kb from CpG island, OpenSea > 4 kb from CpG island
  5. Based on the UCSC classification. CpGs in promoter: CpGs located in TSS200, TSS1500, 5′UTR, or exon 1 (TSS transcription start site)
  6. *Adjusted for all variables except for cell type. §Adjusted for all variables and cell type (CD8T+, CD4T+, NK, B cell, monocytes, granulocytes)