Table III.
Associations between Wnt antagonist methylation and age, sex, MSI status, MSI-associated features and BRAF V600E status in Newfoundland
| Newfoundland | |||||||||
|
DKK1 |
SFRP1 |
||||||||
| Unmethylated (%) | Methylated (%) | ORb (95% CI) | P | Unmethylated (%) | Highly methylated (%) | ORc (95% CI) | Pd | ||
| Age | |||||||||
| <50 | 74 (12.3) | 9 (9.6) | 1.0 | 0.61 | 9 (22.0) | 16 (9.2) | 1.0 | 0.08 | |
| 50+ | 528 (87.7) | 85 (90.4) | 1.3 (0.6–2.7) | 32 (78.0) | 158 (90.8) | 2.8 (1.1–6.8) | |||
| Sex | |||||||||
| Male | 385 (64.0) | 43 (45.7) | 1.0 | 9.21 × 10−4,a | 26 (63.4) | 118 (67.8) | 1.0 | 0.11 | |
| Female | 217 (36.0) | 51 (54.3) | 2.1 (1.4–3.3) | 15 (36.6) | 56 (32.2) | 0.8 (0.4–1.7) | |||
| Location | |||||||||
| Distal | 375 (63.3) | 22 (23.4) | 1.0 | 6.57 × 10−13,a | 17 (41.5) | 114 (65.9) | 1.0 | 0.009 | |
| Proximal | 217 (36.7) | 72 (76.6) | 5.7 (3.4–9.4) | 24 (58.5) | 59 (34.1) | 0.4 (0.2–0.7) | |||
| Histological type | |||||||||
| Non-mucinous | 537 (89.2) | 73 (77.7) | 1.0 | 0.004 | 32 (78.0) | 162 (93.1) | 1.0 | 0.009 | |
| Mucinous | 65 (10.8) | 21 (22.3) | 2.4 (1.4–4.1) | 9 (22.0) | 12 (6.9) | 0.3 (0.1–0.7) | |||
| MSI status | |||||||||
| MSS | 563 (94.3) | 60 (63.8) | 1.0 | 3.87 × 10−15,a | 33 (82.5) | 163 (95.3) | 1.0 | 0.009 | |
| MSI | 34 (5.7) | 34 (36.2) | 9.4 (5.4–16.2) | 7 (17.5) | 8 (4.7) | 0.2 (0.1–0.7) | |||
| MMR protein status | |||||||||
| Intact | 554 (95.4) | 60 (63.8) | 1.0 | 2.32 × 10−16,a | 32 (82.1) | 158 (94.6) | 1.0 | 0.03 | |
| Deficient | 27 (4.6) | 34 (36.2) | 11.6 (6.6–20.6) | 7 (17.9) | 9 (5.4) | 0.3 (0.1–0.8) | |||
| MMR germ line mutation | |||||||||
| No | 587 (97.5) | 92 (97.9) | 1.0 | 1.00 | 38 (92.7) | 172 (98.9) | 1.0 | 0.06 | |
| Yes | 15 (2.5) | 2 (2.1) | 0.9 (0.2–3.8) | 3 (7.3) | 2 (1.1) | 0.2 (0.02–0.9) | |||
| MLH1 methylation | |||||||||
| No | 383 (99.5) | 35 (67.3) | 1.0 | 2.01 × 10−15,a | 23 (100.0) | 103 (99.0) | 1.0 | 0.08 | |
| Yes | 2 (0.5) | 17 (32.7) | 93.0 (20.6–419.2) | 0 (0.0) | 1 (1.0) | 0.2 (0.02–1.3)e | |||
| BRAFV600E | |||||||||
| No | 542 (96.6) | 34 (37.0) | 1.0 | 5.18 × 10−42,a | 36 (94.7) | 148 (91.4) | 1.0 | 0.13 | |
| Yes | 19 (3.4) | 58 (63.0) | 48.7 (26.1–90.8) | 2 (5.3) | 14 (8.6) | 1.7 (0.4–7.8) | |||
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.