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Table 4 Overall and stage-wise association of methylation panels in stool with risk of colorectal neoplasms

From: Fecal DNA methylation markers for detecting stages of colorectal cancer and its precursors: a systematic review

Gene panel

First author, year, Ref. No.

Country

Study group

No.

DNAm assay

OR (95% CI)

p-valuea

CRC stage

N

Stage-specific OR (95% CI)

p-valuea

p-valueb

MGMT, MLH1, and VIM (promoters)

Baek, 2009 [44]

South Korea

NAA

AA

Ad

CRC

Cn

30

22

52

60

37

MSP

14.9 (4.4–50.8)

5.3 (1.5–18.8)

9.5 (3.2–28.2)

19.2 (6.3–58.2)

< 0.001

0.01

< 0.001

< 0.001

I/II

III/IV

35

25

16.0 (4.9–52.8)

25.6 (6.6–99.7)

< 0.001

< 0.001

0.450

ITGA4, SFRP2, and CDKN2A (promoters)

Chang, 2010 [46]

Korea

NAA

AA

Ad

CRC

Cn

17

8

25

30

31

MSP

55.0 (5.9–509.9)

210.0 (11.7–3783.8)

77.1 (8.8–679.2)

70.0 (8.2–594.9)

< 0.001

< 0.001

< 0.001

< 0.001

I/II

III/IV

14

16

54.0 (5.6–524.0)

90.0 (9.1–889.9)

< 0.001

< 0.001

0.694d

SFRP2, GATA4/5, NDRG4, and VIM (promoters)

Lu, 2014 [49]

China

CRC

Cn

56

40

MSP

50.1 (10.6–237.1)

< 0.001

I/II

III/IV

32

24

27.9 (5.8–134.2)

89.6 (5.1–1583.0)c

< 0.001

< 0.001

0.501d

SFRP2 and WIF-1 (promoters)

Zhang, 2014 [50]

China

NAA

AA

Ad

CRC

Cn

20

15

35

48

30

MSP

35.4 (4.0–313.4)

116.0 (10.9–1229.9)

55.6 (6.7–459.5)

125.7 (15.1–1048.2)

< 0.001

< 0.001

< 0.001

< 0.001

I/A

II/B

III/C

IV/D

7

20

14

7

174.0 (9.5–3187.4)

116.0 (11.9–1128.2)

72.5 (7.2–727.6)

295.0 (10.9–7994.2)c

< 0.001

< 0.001

< 0.001

< 0.001

0.605d

SFRP2, TFPI2, NDRG4, and BMP3 (promoters)

Park, 2017 [34]

South Korea

AA

CRC

Cn

36

35

40

MSP

3.2 (1.2–8.3)

20.2 (4.3–95.7)

0.017

< 0.001

I/II

III/IV

17

18

9.2 (1.9–45.5)

45.0 (2.5–798.2)c

0.003

0.000

0.229d

COL4A2 and TLX2 (promoter/exon 1)

Liu, 2019 [40]

China

AA

CRC

Cn

77

80

83

qMSP

43.8 (10.0–190.9)

422.4 (85.0–2098.2)

< 0.001

< 0.001

I/II

III/IV

43

37

249.8 (48.1–1296.4)

1458.0 (128.1–16,600.2)

< 0.001

< 0.001

0.168

  1. Note: Stages I/II/III/IV as per UICC classification and stages A/B/C/D as per Dukes classification
  2. Ref. reference, No. number, DNAm DNA methylation, MSP methylation-specific polymerase chain reaction, qMSP quantitative methylation-specific real-time polymerase chain reaction, n-MSP nested methylation-specific polymerase chain reaction, Hi-SA high-sensitivity assay for bisulfite DNA, LTE linear target enrichment, MSRH methylation-specific reverse hybridization, NAA non-advanced adenoma, AA advanced adenoma, Ad adenoma, Cn control
  3. aStatistical significance for OR
  4. bStatistical significance for association between methylation level and CRC stage
  5. cCalculated using Haldane–Anscombe correction (0.5 added to each cell) [53, 54]
  6. dCalculated using Fisher’s exact test