Table 2.
Associations among the Methylation Status of Candidate Genes, MCSM, MCSHM, and CRC Susceptibility
| Methylation status | Case (%) | Control (%) | Crude OR (95% CI) | p-value | ORadjusted (95% CI)* | p-value | ORadjusted (95% CI)† | p-value |
|---|---|---|---|---|---|---|---|---|
| CA10 | ||||||||
| Um | 47 (10.1) | 146 (29.7) | 1.000 | 1.000 | 1.000 | |||
| Pm | 185 (39.9) | 180 (36.7) | 3.193 (2.167–4.704) | 0.000 | 3.136 (2.117–4.645) | 0.000 | 4.202 (2.348–7.519) | 0.000 |
| Hm1 | 111 (23.9) | 81 (16.5) | 4.257 (2.753–6.583) | 0.000 | 4.197 (2.694–6.540) | 0.000 | 4.913 (2.534–9.527) | 0.000 |
| Hm2 | 53 (11.4) | 61 (12.4) | 2.699 (1.648–4.421) | 0.000 | 2.632 (1.598–4.335) | 0.000 | 2.504 (1.209–5.186) | 0.014 |
| Hm3 | 68 (14.7) | 23 (4.7) | 9.184 (5.164–16.335) | 0.000 | 8.514 (4.743–15.282) | 0.000 | 15.668 (7.341–33.441) | 0.000 |
| Thm | 232 (50.0) | 165 (33.6) | 4.368 (2.973–6.416) | 0.000 | 4.209 (2.848–6.221) | 0.000 | 5.445 (3.075–9.643) | 0.000 |
| Tpm | 417 (89.9) | 345 (70.3) | 3.755 (2.624–5.373) | 0.000 | 3.647 (2.537–5.244) | 0.000 | 4.831 (2.819–8.278) | 0.000 |
| CRH | ||||||||
| Um | 26 (5.6) | 20 (4.1) | 1.000 | 1.000 | 1.000 | |||
| Pm | 165 (35.7) | 143 (29.0) | 0.888 (0.475–1.657) | 0.708 | 0.839 (0.444–1.585) | 0.589 | 0.808 (0.356–1.833) | 0.610 |
| Hm1 | 213 (46.1) | 192 (38.9) | 0.853 (0.461–1.578) | 0.613 | 0.915 (0.489–1.712) | 0.782 | 0.605 (0.264–1.384) | 0.234 |
| Hm2 | 41 (8.9) | 65 (13.2) | 0.485 (0.240–0.979) | 0.043 | 0.504 (0.247–1.029) | 0.060 | 0.188 (0.069–0.513) | 0.001 |
| Hm3 | 17 (3.7) | 73 (14.8) | 0.179 (0.082–0.393) | 0.000 | 0.182 (0.082–0.404) | 0.000 | 0.132 (0.044–0.394) | 0.000 |
| Thm | 271 (58.7) | 330 (66.9) | 0.632 (0.345–1.156) | 0.137 | 0.666 (0.360–1.230) | 0.194 | 0.400 (0.178–0.899) | 0.027 |
| Tpm | 436 (94.4) | 473 (95.9) | 0.709 (0.390–1.288) | 0.259 | 0.721 (0.393–1.324) | 0.291 | 0.542 (0.246–1.194) | 0.128 |
| TMEM132D | ||||||||
| Um | 120 (26.0) | 127 (25.8) | 1.000 | 1.000 | 1.000 | |||
| Pm | 74 (16.0) | 70 (14.2) | 1.119 (0.742–1.688) | 0.593 | 1.024 (0.670–1.563) | 0.914 | 1.428 (0.767–2.659) | 0.261 |
| Hm1 | 151 (32.7) | 148 (30.1) | 1.080 (0.771–1.513) | 0.655 | 1.072 (0.760–1.513) | 0.691 | 1.708 (1.037–2.815) | 0.036 |
| Hm2 | 41 (8.9) | 80 (16.3) | 0.542 (0.345–0.852) | 0.008 | 0.467 (0.293–0.743) | 0.001 | 0.566 (0.288–1.113) | 0.099 |
| Hm3 | 76 (16.5) | 67 (13.6) | 1.200 (0.795–1.813) | 0.385 | 1.087 (0.713–1.658) | 0.698 | 2.696 (1.498–4.852) | 0.001 |
| Thm | 268 (58.0) | 295 (60.0) | 0.961 (0.713–1.297) | 0.797 | 0.908 (0.669–1.234) | 0.539 | 1.542 (0.991–2.400) | 0.055 |
| Tpm | 342 (74.0) | 365 (74.2) | 0.992 (0.742–1.325) | 0.955 | 0.932 (0.693–1.253) | 0.640 | 1.520 (0.988–2.340) | 0.057 |
| CITED4 | ||||||||
| Um | 387 (84.7) | 398 (88.2) | 1.000 | 1.000 | 1.000 | |||
| Pm | 56 (12.3) | 19 (4.2) | 3.031 (1.7680–5.195) | 0.000 | 2.772 (1.604–4.790) | 0.000 | 6.041 (2.785–13.102) | 0.000 |
| Hm1 | 4 (0.9) | 30 (6.7) | 0.137 (0.048–0.393) | 0.000 | 0.134 (0.047–0.386) | 0.000 | 0.423 (0.125–1.438) | 0.168 |
| Hm2 | 8 (1.8) | 4 (0.9) | 2.057 (0.614–6.886) | 0.242 | 2.023 (0.593–6.895) | 0.260 | 2.698 (0.567–12.850) | 0.213 |
| Hm3 | 2 (0.4) | 0 | - | - | - | - | - | - |
| Thm | 14 (3.1) | 34 (7.5) | 0.423 (0.224–0.801) | 0.008 | 0.416 (0.218–0.793) | 0.008 | 1.087 (0.457–2.586) | 0.851 |
| Tpm | 70 (15.3) | 53 (11.8) | 1.358 (0.926–1.993) | 0.117 | 1.270 (0.859–1.877) | 0.231 | 2.962 (1.675–5.239) | 0.000 |
| WT1 | ||||||||
| Um | 145 (31.5) | 195 (40.2) | 1.000 | 1.000 | 1.000 | |||
| Pm | 235 (51.0) | 169 (34.8) | 1.870 (1.396–2.504) | 0.000 | 1.741 (1.291–2.347) | 0.000 | 3.140 (2.024–4.872) | 0.000 |
| Hm1 | 14 (3.0) | 45 (9.3) | 0.418 (0.221–0.791) | 0.007 | 0.391 (0.205–0.748) | 0.005 | 1.507 (0.649–3.496) | 0.340 |
| Hm2 | 62 (13.4) | 69 (14.2) | 1.208 (0.806–1.811) | 0.359 | 1.150 (0.761–1.738) | 0.508 | 1.980 (1.113–3.523) | 0.020 |
| Hm3 | 5 (1.1) | 7 (1.4) | 0.961 (0.299–3.088) | 0.946 | 0.883 (0.269–2.900) | 0.838 | 1.755 (0.416–7.404) | 0.444 |
| Thm | 81 (17.6) | 121 (24.9) | 0.900 (0.632–1.283) | 0.561 | 0.852 (0.593–1.223) | 0.385 | 1.831 (1.100–3.047) | 0.020 |
| Tpm | 316 (68.5) | 290 (59.8) | 1.465 (1.121–1.915) | 0.005 | 1.374 (1.044–1.807) | 0.023 | 2.590 (1.730–3.878) | 0.000 |
| MCSM | ||||||||
| Non-MCSM | 17 (3.8) | 29 (6.7) | 1.000 | 1.000 | 1.000 | |||
| MCSM-L | 182 (40.7) | 208 (48.1) | 1.493 (0.794–2.805) | 0.213 | 1.403 (0.741–2.658) | 0.299 | 1.430 (0.504–4.054) | 0.501 |
| MCSM-H | 248 (55.5) | 195 (45.1) | 2.170 (1.158–4.063) | 0.016 | 1.936 (1.024–3.657) | 0.042 | 4.318 (1.529–12.197) | 0.006 |
| MCSM | 430 (96.2) | 403 (93.3) | 1.820 (0.985–3.363) | 0.056 | 1.659 (0.890–3.092) | 0.111 | 2.528 (0.921–6.939) | 0.072 |
| MCSHM | ||||||||
| Non-MCSHM | 17 (15.0) | 29 (18.0) | 1.000 | 1.000 | 1.000 | |||
| MCSHM-L | 32 (28.3) | 45 (28.0) | 1.213 (0.573–2.570) | 0.614 | 1.180 (0.545–2.557) | 0.675 | 1.153 (0.335–3.969) | 0.821 |
| MCSHM-H | 64 (56.6) | 87 (54.0) | 1.255 (0.636–2.477) | 0.513 | 1.110 (0.551–2.234) | 0.771 | 1.396 (0.438–4.449) | 0.573 |
| MCSHM | 96 (85.0) | 132 (82.0) | 1.241 (0.645–2.386) | 0.518 | 1.133 (0.579–2.217) | 0.716 | 1.297 (0.427–3.942) | 0.647 |
MCSM, multiple CpG site methylation; MCSHM, multiple CpG site heterogeneous methylation; CRC, colorectal cancer; OR, odds ratio; CI, confidence interval; Um, unmethylation; Pm, positive methylation; Hm1, heterogeneous methylation 1; Hm2, heterogeneous methylation 2; Hm3, heterogeneous methylation 3; Thm, total heterogeneous methylation; Tpm, total positive methylation; MCSM-L, low-level MCSM; MCSM-H, high-level MCSM; MCSHM-L, low-level MCSHM; MCSHM-H, high-level MCSHM.
*
ORadjusted, ORs adjusted for body mass index (BMI) and age;
†
ORadjusted, ORs adjusted for BMI, age, fruit, coarse grains, fruit can, pork intestines, fried food, garlic, and braised fish in brown sauce.