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Table 2 Global DNA methylation in peripheral blood of breast cancer cases and healthy controls

From: Blood-based DNA methylation as biomarker for breast cancer: a systematic review

Measurements Author, year [ref] Study design Assay (value) Case no./control no. Case age/control age (y)a Meth (case) Meth (control) p value Main findings
β value van Veldhoven K, 2015 [18] Nested case–control 450 K (EPIC cohort) (mean + SD) 162/162 54.4/54.2 53.00 ± 0.39 53.18 ± 0.35 1.82E−05 Epigenome-wide hypomethylation of DNA in samples from EPIC cohort.
    450 K (NOWAC cohort) (mean + SD) 168/168 55.4/55.4 54.02 ± 0.45 54.02 ± 0.41 0.79
    WBGS (BGS cohort) (mean) 548/548 52/52 48.12 48.3 na
  Severi G, 2014 [19] Nested case–control 450 K (mean + SD) 420/420 64/64 51.86 ± 1.00 51.95 ± 1.01 0.006 Epigenome-wide hypomethylation of DNA in BC patients.
LUMA Kuchiba A, 2014 [36] Case–control LUMA (% DNA meth) 384/384 54.1/53.9 68.9 ± 3.5 70.2 ± 3.4 <0.01 Global genomic hypomethylation in BC patients.
  Xu X, 2012 [29] Case–control LUMA (%) 1055/1101 na/na 57.3 ± 15.7 52.4 ± 16.7 <0.0001 Global promoter hypermethylation in patients.
  Delgado-Cruzata L, 2012 [32] Case–control LUMA (%) 263/321 49.5/48.0 67.1 ± 7.6 67.5 ± 7.3 >0.05 LUMA DNA methylation levels were similar between cases and controls.
5-mdC Choi JY, 2009 [26] Case–control LC-MS (test set) (mean) 19/18 35–75/35–75 3.98 4.33 0.001 Hypomethylation of 5-mdC in BC patients.
    LC-MS (validation set) (mean) 176/173 35–75/35–75 4.18 ± 0.34 4.38 ± 0.36 <0.001
LINE-1 Kitkumthorn N, 2012 [33] Case–control COBRA (%) 36/144 50.28/48.67 40 42 >0.05 No significant differences in LINE-1 methylation between BC cases and healthy controls.
  Xu X, 2012 [29] Case–control Pyrosequencing (mean) 1064/1100 na/na 78.8 78.8 0.94 As above.
  Brennan K, 2012 [17]   Pyrosequencing (mean and IQR)       As above.
   Case–control BGS cohort 241/242 54/54 79.0 (78.1–79.9) 79.0 (77.9–80.1) 0.96
   Case–control EPIC cohort 232/263 52/52 75.2 (73.9–76.3) 75.1 (73.9–76.3) 0.89
   Nested case–control KConFab cohort 153/218 50/60 76.6 (75.2–77.6) 76.0 (74.3–78.0) 0.2
  Wu HC, 2012 [31] Case–control MethyLight (%) 265/333 49.5/48.0 107.4 ± 63.6 108.5 ± 59.1 >0.05 As above.
    Pyrosequencing (mean) 279/340 49.5/48.0 74.5 ± 3.0 74.5 ± 2.6 >0.05
  Cho YH, 2010 [27] Case–control MethyLight (%) 40/40 50.8/48.3 70 78 >0.05 As above.
  Choi JY, 2009 [26] Case–control Pyrosequencing (mean) 19/18 35–75/35–75 74.7 73.9 0.176 As above.
  Deroo LA, 2014 [38]b Nested case–control Pyrosequencing 294/646 57.9/na na na na As above.
Sat2 Wu HC, 2012 [31] Case–control MethyLight (%) 266/333 49.5/48.0 41.3 ± 24.4 43.5 ± 32.9 >0.05 No significant differences in Sat2 methylation between BC cases and healthy controls.
  Cho YH, 2010 [27] Case–control MethyLight (%) 40/40 50.8/48.3 125 150 0.01 Hypomethylation of Sat2 inpatients.
Alu Wu HC, 2012 [31] Case–control MethyLight (%) 266/334 49.5/48.0 95.5 ± 36.6 98.7 ± 51.5 >0.05 No significant differences in Alu methylation between BC cases and healthy controls.
  Cho YH, 2010 [27] Case–control MethyLight (%) 40/40 50.8/48.3 58 61 >0.05 As above.
[3H]-methyl Delgado-Cruzata L, 2012 [32] Case–control [3H]-Methyl acceptance assay 233/295 49.6/48.2 97,111 ± 76,348 88,030 ± 70,841 <0.05 Global genomic hypomethylation in BC patients (more [3H]-methyl acceptance).
  1. The numbers in italic are extracted from boxplot or scatter plots
  2. 450K Infinium HumanMethylation 450K Beadchips, WGBS whole genome bisulfite sequencing, LUMA luminometric methylation assay, COBRA combined bisulfite restriction analysis, 5-mdC 5-methyldeoxycytosine, na not available
  3. aAge indicates mean age or range
  4. bThe mean DNA methylation level of BC cases and controls is not available; the study only reported the results of the quartile analysis