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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
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Clinical Epigenetics

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