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Table 4 Adjusted differences in mean % methylation comparing adjacent (referent) to cancer tissue, overall and stratified by ER/PR status

From: Exploring DNA methylation changes in promoter, intragenic, and intergenic regions as early and late events in breast cancer formation

 

All samples

 

ER/PR Positive

 

ER/PR Negative

 

Na

Diff.b

95 % CIc

P-Valued

Na

Diff.b

95 % CIc

P-Valued

Na

Diff.b

95 % CIc

P-Valued

Promoter regions

            

  BRCA1

198

1.7

(0, 4)

NS

136

1

(-1, 4)

NS

62

3

(0, 8)

0.09

  CD44e

54

0.5

(0, 1)

NS

32

0

(-0.4, 1)

NS

22

0

(0,2)

NS

  ESR1e

54

-1.5

(-3, 0)

0.099

32

-1

(-4, 1)

NS

22

-2

(-4, 1)

NS

  GSTM2

212

16.8

(13, 21)

< 0.0001

146

10

(6, 16)

< 0.0001

66

32

(24, 38)

< 0.0001

  GSTP1

227

8.3

(6, 12)

< 0.0001

159

9

(6, 14)

< 0.0001

68

6

(2, 12)

0.016

  MAGEA1e

54

-14.5

(-22, -9)

< 0.0001

32

-22

(-30, -14)

< 0.0001

22

-4

(-12, 3)

NS

  MSI1e

54

4.7

(2, 8)

0.005

32

4

(1, 10)

0.057

22

5

(1, 9)

0.01

  NFE2L3e

54

5.6

(-4, 16)

NS

32

19

(9, 31)

0.001

22

-15

(-26, -4)

0.01

  RASSF1A

234

23.5

(19, 28)

< 0.0001

160

26

(21, 31)

< 0.0001

74

18

(12, 25)

< 0.0001

  RUNX3

227

6.6

(4, 9)

< 0.0001

156

9

(6, 11)

< 0.0001

71

2

(-1, 7)

NS

  SIX3

221

10.9

(9, 14)

< 0.0001

151

10

(7, 14)

< 0.0001

70

13

(8, 19)

< 0.0001

  TFF1

230

-21.6

(-26, -17)

< 0.0001

159

-25

(-30, -19)

< 0.0001

71

-14

(-23, -5)

0.002

Upstream of promoter

            

  EN1

230

13.1

(10, 17)

< 0.0001

158

12

(8, 16)

< 0.0001

72

16

(9, 24)

< 0.0001

  PAX3

230

7.3

(5, 10)

< 0.0001

159

6

(4, 9)

< 0.0001

71

10

(6, 15)

< 0.0001

  PITX2e

54

7.8

(4, 11)

< 0.0001

32

7

(3, 10)

< 0.0001

22

10

(1, 16)

0.026

  SGK1

233

9.8

(8, 12)

< 0.0001

160

9

(7, 12)

< 0.0001

73

11

(7, 16)

< 0.0001

Introns

            

  APC

221

12.3

(9, 16)

< 0.0001

153

12

(8, 16)

< 0.0001

68

15

(9, 22)

< 0.0001

  EGFR

235

12

(9, 15)

< 0.0001

161

15

(11, 18)

< 0.0001

74

6

(2, 11)

0.009

  LHX2e

54

8.1

(2, 15)

0.017

32

8

(3, 13)

0.006

22

9

(-5, 22)

NS

  RFX1

235

19.8

(17, 23)

< 0.0001

161

20

(16, 23)

< 0.0001

74

21

(16, 26)

< 0.0001

  SOX9

231

6.2

(3, 9)

< 0.0001

158

6

(3, 10)

< 0.0001

73

6

(1, 13)

0.031

DNA Repeats

            

  LINE-1

238

-1.5

(-2, -1)

< 0.0001

162

-2

(-3, -1)

< 0.0001

76

-1

(-3, 0)

0.074

  Sat2

237

-5.4

(-9, -2)

0.001

161

-6

(-10, -2)

0.003

76

-5

(-10, 1)

0.109

  1. aNumber of samples analyzed; the small differences in numbers of samples in this table compared to Table 3 are due to missing data on ER/PR status
  2. bDifference in mean percent methylation (cancer and adjacent) was estimated via linear regression model with generalized estimating equations to account for within-patient covariance
  3. cBias corrected, bootstrapped 95 % confidence intervals (CI) were estimated via 1000 bootstrap replications to account for skewed methylation distributions
  4. dApproximate p-value estimated from a Wald test of the normal-based bootstrapped estimate over its standard error. P-values > 0.1 are suppressed
  5. eThese seven assays were not pursued beyond the pilot phase and therefore have considerably fewer cancer and adjacent tissue samples analyzed
  6. All estimates of mean percent methylation are adjusted for age, race/ethnicity, stage at diagnosis, tumor grade, and either adjusted for or stratified by ER/PR status