Table II.
Associations between Wnt antagonist methylation and age, sex, MSI status, MSI-associated features and BRAF V600E status in Ontario
| Ontario | ||||||||
|
DKK1 |
SFRP1 |
|||||||
| Unmethylated (%) | Methylated (%) | ORb (95% CI) | P | Unmethylated (%) | Highly methylated (%) | ORc (95% CI) | Pd | |
| Age | ||||||||
| <50 | 55 (11.5) | 6 (8.5) | 1.0 | 0.55 | 9 (32.1) | 9 (6.4) | 1.0 | 0.001a |
| 50+ | 422 (88.5) | 65 (91.5) | 1.4 (0.6–3.4) | 19 (67.9) | 132 (93.6) | 7.0 (2.5–19.7) | ||
| Sex | ||||||||
| Male | 266 (55.8) | 20 (28.2) | 1.0 | 1.96 × 10−5,a | 9 (32.1) | 84 (59.6) | 1.0 | 0.02 |
| Female | 211 (44.2) | 51 (71.8) | 3.2 (1.9–5.6) | 19 (67.9) | 57 (40.4) | 0.3 (0.1–0.8) | ||
| Location | ||||||||
| Distal | 311 (65.9) | 21 (30.9) | 1.0 | 8.38 × 10−8,a | 15 (55.6) | 98 (70.0) | 1.0 | 0.05 |
| Proximal | 161 (34.1) | 47 (69.1) | 4.3 (2.5–7.5) | 12 (44.4) | 42 (30.0) | 0.5 (0.2–1.2) | ||
| Histological type | ||||||||
| Non-mucinous | 395 (89.0) | 50 (76.9) | 1.0 | 0.01 | 22 (81.5) | 118 (91.5) | 1.0 | 0.18 |
| Mucinous | 49 (11.0) | 15 (23.1) | 2.4 (1.3–4.6) | 5 (18.5) | 11 (8.5) | 0.4 (0.1–1.3) | ||
| MSI status | ||||||||
| MSS | 427 (90.5) | 29 (40.8) | 1.0 | 5.46 × 10−20,a | 22 (81.5) | 132 (94.3) | 1.0 | 1.33 × 10−4,a |
| MSI | 45 (9.5%) | 42 (59.2%) | 13.7 (7.8–24.2) | 5 (18.5) | 8 (5.7) | 0.3 (0.1–0.9) | ||
| MMR protein status | ||||||||
| Intact | 419 (92.1) | 29 (42.6) | 1.0 | 3.94 × 10−20,a | 22 (81.5) | 126 (94.0) | 1.0 | 0.002a |
| Deficient | 36 (7.9) | 39 (57.4) | 15.7 (8.7–28.2) | 5 (18.5) | 8 (6.0) | 0.3 (0.1–0.9) | ||
| MMR germ line mutation | ||||||||
| No | 139 (92.1) | 42 (95.5) | 1.0 | 0.74 | 7 (70.0) | 41 (100.0) | 1.0 | 0.009 |
| Yes | 12 (7.9) | 2 (4.5) | 0.6 (0.1–2.6) | 3 (30.0) | 0 (0.0) | 0.2 (0.04–0.7)e | ||
| MLH1 methylation | ||||||||
| No | 462 (97.1) | 33 (46.5) | 1.0 | 2.32 × 10−27,a | 27 (96.4) | 135 (95.7) | 1.0 | 0.01 |
| Yes | 14 (2.9) | 38 (53.5) | 38.0 (18.7–77.1) | 1 (3.6) | 6 (4.3) | 1.2 (0.1–10.4) | ||
| BRAF V600E | ||||||||
| No | 437 (94.4) | 29 (43.9) | 1.0 | 2.82 × 10−22,a | 26 (96.3) | 128 (93.4) | 1.0 | 0.02 |
| Yes | 26 (5.6) | 37 (56.1) | 22.4 (11.5–40.1) | 1 (3.7) | 9 (6.6) | 1.8 (0.2–15.1) | ||
a
Significant P-value after Bonferroni correction (P < 5.55 × 10−3).
b
Odds ratio for DKK1 methylated versus DKK1 unmethylated. Corresponding P-value indicated.
c
Odds ratio for SFRP1 highly methylated versus SFRP1 unmethylated.
d
P-value for the trend over all three SFRP1 methylation groups. See supplementary Table 1 (available at Carcinogenesis Online) for representation of SFRP1 low methylation.
e
Due to zero cell count, odds ratio represents SFRP1 methylated versus SFRP1 unmethylated.