Table 4.
Diagnostic performance of methylation panels.
| Gene Panel | First author, Year [Ref. No.] |
No. Cases/Controls |
Age(yrs) Cases/ Controls |
DNAm Assay | AUC | Classification | OR (95%CI) |
p- Value * |
|---|---|---|---|---|---|---|---|---|
| Hypomethylation | ||||||||
| PER1/PER3 | Alexander, 2017 [43] | 38/69 | -- | MS-PCR | -- | -- | 0.50 (0.22–1.15) a | 0.10 |
| PER1/APBA1 | Alexander, 2017 [43] | 38/69 | -- | MS-PCR | -- | -- | 0.59 (0.26–1.33) a | 0.20 |
| PER3/APBA1 | Alexander, 2017 [43] | 38/69 | -- | MS-PCR | -- | -- | 0.27 (0.09–0.81) a | 0.02 |
| PER1/PER3/APBA1 | Alexander, 2017 [43] | 38/69 | -- | MS-PCR | -- | -- | 0.57 (0.25–1.27) a | 0.17 |
| Hypermethylation | ||||||||
|
MCSM
(WT1, CA10, CITED4 & TMEM132D) |
Gao, 2018 [37] | 466/507 | 60.1/56.7 | MS-HRM | -- | Non-MCSM | 1.00 b | |
| (no methylated gene) (ref) | ||||||||
| MCSM-L (≤2 methylated genes) | 1.43 (0.50–4.05) | 0.50 | ||||||
| MCSM-H (≥3 methylated genes) | 4.32 (1.53–12.2) | 0.01 | ||||||
| MCSM | 2.53 (0.92–6.94) | 0.07 | ||||||
|
MRS_10
(APC+CDH1+ CDKN2A+DAPK1+ IGF2+MGMT+ MINT31+MLH1+ NEUROG1+WIF1) |
Liu, 2017 [39] | 428/428 | 59.4/59.4 | MS-HRM | 0.69 (0.66–0.73), p < 0.0001 |
Low predicted probability ≤0.5 (ref) | 1.00 c | |
| Medium | 3.85 (2.72–5.45) | <0.0001 | ||||||
| (0.5 < predicted probability ≤ 0.7) | ||||||||
| High | 6.51 (3.77–11.27) | <0.0001 | ||||||
| (predicted probability >0.7) | ||||||||
| Medium or High | 4.39 (3.19–6.05) | <0.0001 | ||||||
| Markers-only model (cg04036920, cg14472551 & cg12459502) | Heiss, 2017 [19] | SS: 46/46 CS: 93/94 |
67/67 65/65 |
HM 450K | 0.69 (0.55, 0.82) d 0.73 (0.63, 0.83) d |
|||
| Full model (combining sex, age, cg04036920, cg14472551 & cg12459502) | Heiss, 2017 [19] | SS: 46/46 CS: 93/94 |
67/67 65/65 |
HM 450K | 0.69 (0.54, 0.83) d 0.73 (0.61, 0.82) d |
|||
|
MCSM
(AOX-1, RARB2, RERG, ADAMTS9, IRF4, & FOXE-1) |
Luo, 2016 [40] | 421/506 | 59.5/56.6 | MS-HRM | -- | Non-MCSM | 1.00 e | |
| (no methylated gene) (ref) | ||||||||
| MCSM-L (1 methylated gene) | 1.23 (0.87–1.75) | 0.24 | ||||||
| MCSM-H (≥2 methylated genes | 1.79 (1.28–2.52) | 0.00 | ||||||
| (except for RARB2)) | ||||||||
| MCSM | 1.50 (1.11–2.03) | 0.01 |
a Crude OR (95% CI) for dichotomized methylation of gene panel and adenoma risk; coding of methylation status seems erroneous and could not be clarified. b ORs adjusted for BMI, age, fruit, coarse grains, fruit can, pork intestines, fried food, garlic, and braised fish in brown sauce. c ORs adjusted for age, gender, BMI, occupational physical activity, smoking, and consumption of coarse grains, fish stewed with brown sauce, fried food, leftovers, and pork. d Methylation levels were adjusted for leukocyte composition and batch effects. e Model adjusted for age, BMI, occupation and family history of cancer. p-value *: statistical significance for OR. Abbreviations: Ref., Reference; No., Number; DNAm, DNA methylation; OR, Odds Ratio; CI, Confidence Interval; SS, Screening Setting; CS, Clinical setting; MRS, methylation risk score; MCSM, multiple CpG site methylation; HM-450K., Human Methylation 450k; MS-PCR, Methylation Specific Polymerase Chain Reaction; MS-HRM, Methylation-sensitive High-resolution Melting.