Table 4.
Associations of DNA methylation aging markers with CRC-specific mortality
| Markers | Categories | All stages | Stage I and II | Stage III | Stage IV | P for interaction | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| ndeath/ncases | HR (95% CI)* | ndeath/ncases | HR (95% CI)# | ndeath/ncases | HR (95% CI)# | ndeath/ncases | HR (95% CI)# | |||
| AgeAccelHorvath | Tertile 1 | 203/732 | 1.00 (Ref.) | 34/362 | 1.00 (Ref.) | 75/257 | 1.00 (Ref.) | 93/105 | 1.00 (ref.) | – |
| Tertile 2 | 184/731 | 1.03 (0.83, 1.28) | 32/401 | 0.88 (0.54, 1.45) | 69/234 | 1.02 (0.73, 1.42) | 82/91 | 1.11 (0.80, 1.52) | – | |
| Tertile 3 | 209/728 | 1.17 (0.94, 1.46) | 49/390 | 1.67 (1.06, 2.65) | 67/230 | 1.17 (0.83, 1.66) | 92/109 | 0.95 (0.68, 1.31) | – | |
| Per SD increase | 596/2191 | 1.04 (0.95, 1.13) | 115/1153 | 1.17 (0.97, 1.41) | 211/721 | 1.07 (0.93, 1.24) | 267/305 | 0.94 (0.81, 1.08) | 0.256 | |
| AgeAccelHannum | Tertile 1 | 173/732 | 1.00 (Ref.) | 28/384 | 1.00 (Ref.) | 77/266 | 1.00 (Ref.) | 68/78 | 1.00 (ref.) | – |
| Tertile 2 | 204/731 | 0.93 (0.73, 1.17) | 45/386 | 1.46 (0.89, 2.40) | 61/234 | 0.82 (0.57, 1.18) | 98/110 | 0.88 (0.60, 1.29) | – | |
| Tertile 3 | 219/728 | 1.06 (0.83, 1.36) | 42/383 | 1.24 (0.72, 2.12) | 73/221 | 1.13 (0.78, 1.65) | 101/117 | 0.90 (0.60, 1.35) | – | |
| Per SD increase | 596/2191 | 1.07 (0.97, 1.19) | 115/1153 | 1.05 (0.84, 1.31) | 211/721 | 1.10 (0.94, 1.29) | 267/305 | 1.02 (0.87, 1.20) | 0.258 | |
| DNAmMRscore | Tertile 1 | 166/733 | 1.00 (Ref.) | 31/409 | 1.00 (Ref.) | 63/241 | 1.00 (Ref.) | 72/83 | 1.00 (ref.) | |
| Tertile 2 | 176/729 | 0.90 (0.68, 1.17) | 38/395 | 1.07 (0.61, 1.86) | 53/229 | 0.81 (0.53, 1.25) | 84/101 | 0.82 (0.56, 1.21) | ||
| Tertile 3 | 254/729 | 1.54 (1.11, 2.15) | 46/349 | 1.38 (0.71, 2.66) | 95/251 | 1.61 (1.00, 2.57) | 111/121 | 1.21 (0.77, 1.88) | – | |
| Per SD increase | 596/2191 | 1.30 (1.11, 1.53) | 115/1153 | 1.34 (0.99, 1.81) | 211/721 | 1.36 (1.10, 1.67) | 267/305 | 1.06 (0.86, 1.29) | 0.041 | |
| AgeAccelPheno | Tertile 1 | 168/732 | 1.00 (Ref.) | 30/389 | 1.00 (Ref.) | 72/262 | 1.00 (Ref.) | 65/78 | 1.00 (ref.) | – |
| Tertile 2 | 196/731 | 1.20 (0.96, 1.51) | 40/394 | 1.08 (0.66, 1.78) | 63/231 | 1.01 (0.70, 1.45) | 93/101 | 1.51 (1.06, 2.14) | – | |
| Tertile 3 | 232/728 | 1.25 (0.98, 1.59) | 45/370 | 1.38 (0.84, 2.29) | 76/228 | 1.26 (0.89, 1.79) | 109/126 | 1.26 (0.88, 1.81) | – | |
| Per SD increase | 596/2191 | 1.15 (1.04, 1.27) | 115/1153 | 1.18 (0.97, 1.42) | 211/721 | 1.22 (1.06, 1.42) | 267/305 | 1.08 (0.92, 1.25) | 0.281 | |
| AgeAccelGrim | Tertile 1 | 175/732 | 1.00 (Ref.) | 32/404 | 1.00 (Ref.) | 80/257 | 1.00 (Ref.) | 63/70 | 1.00 (ref.) | – |
| Tertile 2 | 188/731 | 0.92 (0.73, 1.17) | 38/379 | 1.14 (0.68, 1.93) | 60/245 | 0.79 (0.54, 1.15) | 90/103 | 0.92 (0.64, 1.34) | – | |
| Tertile 3 | 233/728 | 1.28 (0.84, 1.93) | 45/370 | 1.53 (0.85, 2.73) | 71/219 | 1.19 (0.80, 1.77) | 114/132 | 0.94 (0.65, 1.37) | – | |
| Per SD increase | 596/2191 | 1.26 (1.09, 1.45) | 115/1153 | 1.24 (0.99, 1.56) | 211/721 | 1.10 (0.92, 1.31) | 267/305 | 1.18 (1.00, 1.40) | 0.036 | |
AgeAccel, age acceleration; CI, confidence interval; DNAm, DNA methylation; HR, hazard ratio; MRscore, mortality risk score
Numbers printed in bold: statistically significantly different from 1 (P < 0.05)
*Overall HR was adjusted for age, sex, batch effects, tumor stage and leukocyte composition (Houseman’s algorithm)
#Stage-specific HR was adjusted for age, sex, batch effects and leukocyte composition (Houseman’s algorithm)