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Table 2 Interacting effects of 25(OH)D and methylation at CpG sites in vitamin D-related genes on the 5-year risk of breast cancer (1024 cases, 1270 from subcohort, including 46 additional casesa): ratio of hazard ratios and 95% confidence intervals for CpGs with statistically significant interactions (p < 0.05)

From: Vitamin D, DNA methylation, and breast cancer

Rank

CpG site

Gene / location type

HR (95% CI) for methylation-breast cancer association

HR (95% CI) for methylation-breast cancer association, if 25(OH)D ≤ 38.0 ng/mL

HR (95% CI) for methylation-breast cancer association, if 25(OH)D > 38.0 ng/mL

Ratio of Hazard Ratios (95% CI)b

Interaction p value

1

cg21201924

RXRA / body

1.00 (0.96–1.04)

0.97 (0.93–1.01)

1.18 (1.08–1.29)

1.22 (1.10–1.34)

7.0 × 10−5

2

cg13786567

RXRA / body

1.01 (0.94–1.08)

0.94 (0.87–1.02)

1.34 (1.12–1.60)

1.42 (1.17–1.73)

4.0 × 10−4

3

cg02127980

RXRA / body

1.00 (0.94–1.06)

0.95 (0.88–1.01)

1.22 (1.07–1.38)

1.29 (1.11–1.49)

7.0 × 10−4

4

cg12978433

CYP24A1 / 1st exon

1.01 (0.98–1.04)

1.04 (1.00–1.07)

0.93 (0.88–0.98)

0.90 (0.84–0.96)

9.0 × 10−4

5

cg14154547c

RXRA / body

0.96 (0.90–1.03)

0.91 (0.84–0.98)

1.17 (1.01–1.36)

1.29 (1.09–1.53)

0.003

6

cg18956481c

CYP24A1 / 5´ UTR

0.99 (0.97–1.02)

1.01 (0.99–1.04)

0.93 (0.88–0.98)

0.92 (0.86–0.98)

0.006

7

cg13510651c

RXRA / body

0.99 (0.93–1.06)

0.95 (0.88–1.02)

1.18 (1.03–1.35)

1.24 (1.06–1.45)

0.007

8

cg14236758

RXRA / body

1.00 (0.94–1.06)

0.96 (0.90–1.03)

1.19 (1.03–1.37)

1.23 (1.05–1.44)

0.01

9

cg09253762

CYP27B1 / TSS1500

0.99 (0.95–1.04)

0.96 (0.91–1.01)

1.12 (1.01–1.24)

1.16 (1.04–1.31)

0.01

10

cg18482822c

DHCR7 / body

1.02 (0.97–1.06)

0.99 (0.93–1.04)

1.13 (1.02–1.24)

1.14 (1.02–1.27)

0.02

11

cg05072492c

NADSYN1 / TSS1500

1.01 (0.96–1.06)

0.97 (0.92–1.03)

1.11 (1.00–1.24)

1.15 (1.01–1.29)

0.03

12

cg11035813c

DHCR7 / TSS1500

1.02 (0.98–1.07)

1.00 (0.95–1.05)

1.13 (1.02–1.24)

1.13 (1.01–1.26)

0.03

13

cg14854850

VDR / 3´ UTR

0.99 (0.94–1.03)

1.02 (0.97–1.07)

0.90 (0.82–0.99)

0.89 (0.79–0.99)

0.03

14

cg25588697c

DHCR7 / body

1.01 (0.95–1.08)

0.96 (0.89–1.05)

1.14 (1.00–1.30)

1.18 (1.01–1.38)

0.04

15

cg10592901

VDR / body

1.04 (1.01–1.07)

1.06 (1.03–1.10)

0.98 (0.92–1.05)

0.92 (0.86–1.00)

0.04

16

cg12474705c

NADSYN1 / body

0.96 (0.92–1.01)

0.99 (0.94–1.05)

0.88 (0.80–0.98)

0.89 (0.79–1.00)

0.04

17

cg16984335c

CYP27B1 / body

1.00 (0.96–1.04)

1.02 (0.97–1.06)

0.92 (0.83–1.00)

0.90 (0.81–1.00)

0.05

18

cg13941235

RXRA / body

1.00 (0.97–1.02)

0.98 (0.95–1.01)

1.04 (0.99–1.10)

1.06 (1.00–1.13)

0.05

  1. CI confidence interval, HR hazard ratio, TSS1500 within 1500 basepairs upstream of the transcription start site, UTR Untranslated region
  2. aAfter excluding those with missing covariate information
  3. bChange in the methylation-breast cancer association for being in the 4th quartile of 25-hydroxyvitamin D (25(OH)D) (≥ 38.0 ng/mL) versus the first three (< 38.0 ng/mL)—a value > 1.00 indicates that the estimated HR for the methylation-breast cancer association is higher among those with higher 25(OH)D levels; similarly, an RHR < 1.00 indicates that the estimated HR for the methylation-breast cancer association is higher among those with lower 25(OH)D levels
  4. cIntraclass correlation coefficient < 0.5