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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