Table 3 Gene-specific methylation in peripheral blood DNA in breast cancer cases and controls investigated in more than one study

BRCA1

Cho YH, 2015 [39]

MethyLight (%)

1021/1036

na/na

12

10

>0.05

Higher frequency of methylated BRCA1 in BC patients was observed in all six studies.

Gupta S, 2014 [37]

MS-HRM (%)

66/36

48.8/56.1

22.7

5.6

0.03

Bosviel R, 2012 [30]

QMSP (%)

902/990

47.1/45.9

47.1 (46.1–48.1)

45.9 (45.0–46.8)

0.08

Wong EM, 2011 [20]

MS-HRM (%)

255/169

<40/<40

10.9

3.6

0.004

Iwamoto T, 2011 [16]

MSP (%)

200/200

50/50

21.5

13.5

0.045

Cho YH, 2010 [27]

MethyLight (%)

40/40

50.8/48.3

8

5

>0.05

Snell C, 2008 [24]

MethyLight (%)

7/7

35–51/35–51

42.9

14.3

<0.05

ATM

Brennan K, 2012 [17]

Pyrosequencing ATM (mvp2a)

Hypermethylation of ATM (intragenic repetitive element) in BC patients was observed in two studies.

BGS cohort (mean and IQR)

249/248

54/54

76.8 (70.9–82.7)

76.4 (70.2–80.2)

0.02

EPIC cohort (mean and IQR)

235/283

52/52

75.7 (70.0–80.8)

76.1 (70.5–80.6)

0.4

KConFab cohort (mean and IQR)

156/210

50/60

81.8 (75.8–86.5)

76.9 (71.6–81.5)

4.87 × 10⁻⁶

Pyrosequencing ATM (mvp2b)

BGS cohort (mean and IQR)

248/234

54/54

91.4 (85.6–95.0)

91.0 (87.0–94.8)

0.61

EPIC cohort (mean and IQR)

240/287

52/52

92.3 (88.3–95.7)

92.2 (87.3–95.2)

0.36

KConFab cohort (mean and IQR)

162/208

50/60

92.3 (82.4–96.5)

92.6 (87.2–96.3)

0.24

Flanagan JM, 2009 [15]

Pyrosequencing (mean and IQR)

190/190

62.8/62.8

91.4 (72.8–98.4)

89.8 (53.0–98.0)

0.002

IGF2

Harrison K, 2015 [41]

Pyrosequencing (mean ± SD)

189/363

56/56

48.94 ± 5.61

48.15 ± 5.77

0.123

Two studies reported no significant differences in methylation of IGF2 between BC cases and healthy controls.

Ito Y, 2008 [25]

EPIC-Norfolk cohort

228/460

60.5/60.3

6.6

6.3

0.91

ABC cohort

338/84

52.6/43.2

5.6

7.1

0.65

CDH1

Cho YH, 2015 [39]

MethyLight (%)

1021/1036

na/na

58

66

>0.05

Three studies observed no significant differences in methylation of CDH1 between BC cases and controls.

Zmetakova I, 2013 [42]

Pyrosequencing (mean ± SD)

34/50

41–90/20–78

9.64 ± 2.10

9.02 ± 1.60

0.698

Cho YH, 2010 [27]

MethyLight (%)

40/40

50.8/48.3

8

8

>0.05

ESR1

Zmetakova I, 2013 [42]

Pyrosequencing (mean ± SD)

34/50

41–90/20–78

4.09 ± 1.44

3.22 ± 0.86

0.026

Zmetakova I et al. reported higher methylation of ESR1 in patients, while Widschwendter. M et al. observed no significant difference.

Widschwendter M, 2008 [14]

MethyLight (%)

320/676

50–74/50–74

12.2

13.5

0.645

SYK

Zmetakova I, 2013 [42]

Pyrosequencing (mean ± SD)

34/50

41–90/20–78

1.15 ± 0.44

1.06 ± 0.24

0.638

Both studies observed no significant differences in methylation of SYK between BC cases and controls.

Widschwendter M, 2008 [14]

MethyLight (%)

320/676

50–74/50–74

2.2

2.4

0.889

TIMP3

Zmetakova I, 2013 [42]

Pyrosequencing

34/50

41–90/20–78

3.65 ± 2.55

2.50 ± 0.81

0.036

Zmetakova I et al. reported higher methylation of TIMP3 in patients, while Widschwendter. M et al. observed no significant difference.

Widschwendter M, 2008 [14]

MethyLight (%)

320/676

50–74/50–74

12.5

14.2

0.511

RARB

Cho YH, 2015 [39]

MethyLight (%)

1021/1036

na/na

33

39

>0.05

Two studies reported no significant differences in methylation of RARB between BC cases and healthy controls.

Cho YH, 2010 [27]

MethyLight (%)

40/40

50.8/48.3

10

10

>0.05

APC

Zmetakova I, 2013 [42]

Pyrosequencing (mean ± SD)

34/50

41–90/20–78

1.68 ± 1.04

1.28 ± 0.57

0.082

Two studies reported no significant differences in methylation of APC between BC cases and healthy controls.

Cho YH, 2010 [27]

MethyLight (%)

40/40

50.8/48.3

0

0

>0.05

RASSF1A

Zmetakova I, 2013 [42]

Pyrosequencing (mean ± SD)

34/50

41–90/20–78

1.00 ± 0.00

1.04 ± 0.28

0.475

Two studies reported no significant differences in methylation of RASSF1A between BC cases and healthy controls.

Cho YH, 2010 [27]

MethyLight (%)

40/40

50.8/48.3

8

3

>0.05