Table 4.
Colorectal Cancer-Specific and Overall Mortality in Relation to Tumor Molecular Features.
| CRC-specific mortality | Overall mortality | |||||
|---|---|---|---|---|---|---|
| No. of cases | No. of events | Multivariable HRa (95% CI) | No. of cases | No. of events | Multivariable HRa (95% CI) | |
| Overall | ||||||
| MSI status | ||||||
| Non-MSI-high | 9474 | 2351 | 1 (reference) | 10141 | 4477 | 1 (reference) |
| MSI-high | 1978 | 167 | 0.35 (0.29–0.42) | 2081 | 726 | 0.72 (0.66–0.80) |
| CIMP status | ||||||
| CIMP-low/negative | 7115 | 1674 | 1 (reference) | 7701 | 3370 | 1 (reference) |
| CIMP-high | 1367 | 284 | 1.10 (0.94–1.29) | 1509 | 724 | 1.14 (1.03–1.27) |
| BRAF mutation status | ||||||
| BRAF wild-type | 9602 | 2164 | 1 (reference) | 10252 | 4324 | 1 (reference) |
| BRAF mutant | 1207 | 269 | 1.37 (1.18–1.61) | 1315 | 648 | 1.14 (1.03–1.26) |
| KRAS mutation status | ||||||
| KRAS wild-type | 6018 | 1345 | 1 (reference) | 6494 | 2849 | 1 (reference) |
| KRAS mutant | 2918 | 812 | 1.11 (1.01–1.22) | 3269 | 1538 | 1.02 (0.96–1.09) |
| Stage I | ||||||
| MSI status | ||||||
| Non-MSI-high | 2239 | 148 | 1 (reference) | 2361 | 763 | 1 (reference) |
| MSI-high | 453 | 11 | 0.53 (0.27–1.04) | 473 | 136 | 1.04 (0.83–1.30) |
| CIMP status | ||||||
| CIMP-low/negative | 1693 | 104 | 1 (reference) | 1792 | 585 | 1 (reference) |
| CIMP-high | 281 | 11 | 1.31 (0.66–2.59) | 310 | 104 | 1.16 (0.88–1.54) |
| BRAF mutation status | ||||||
| BRAF wild-type | 2284 | 145 | 1 (reference) | 2400 | 783 | 1 (reference) |
| BRAF mutant | 225 | 5 | 1.40 (1.13–1.73) | 247 | 81 | 0.71 (0.54–0.94) |
| KRAS mutation status | ||||||
| KRAS wild-type | 1496 | 85 | 1 (reference) | 1582 | 535 | 1 (reference) |
| KRAS mutant | 659 | 80 | 1.24 (0.86–1.78) | 711 | 255 | 1.01 (0.87–1.18) |
| Stage II and III | ||||||
| MSI status | ||||||
| Non-MSI-high | 5428 | 1205 | 1 (reference) | 5826 | 2377 | 1 (reference) |
| MSI-high | 1287 | 108 | 0.33 (0.26–0.41) | 1362 | 472 | 0.70 (0.62–0.79) |
| CIMP status | ||||||
| CIMP-low/negative | 4189 | 891 | 1 (reference) | 4551 | 1833 | 1 (reference) |
| CIMP-high | 888 | 149 | 1.12 (0.89–1.39) | 984 | 451 | 1.29 (1.11–1.49) |
| BRAF mutation status | ||||||
| BRAF wild-type | 5628 | 1130 | 1 (reference) | 6030 | 2334 | 1 (reference) |
| BRAF mutant | 1014 | 776 | 1.51 (1.16–1.96) | 850 | 411 | 1.10 (0.95–1.26) |
| KRAS mutation status | ||||||
| KRAS wild-type | 3525 | 691 | 1 (reference) | 3833 | 1522 | 1 (reference) |
| KRAS mutant | 1762 | 438 | 1.26 (1.11–1.43) | 1929 | 837 | 1.10 (1.01–1.21) |
| Stage IV | ||||||
| MSI status | ||||||
| Non-MSI-high | 1106 | 866 | 1 (reference) | 1218 | 1018 | 1 (reference) |
| MSI-high | 64 | 31 | 0.44 (0.30–0.64) | 71 | 48 | 0.54 (0.39–0.74) |
| CIMP status | ||||||
| CIMP-low/negative | 741 | 581 | 1 (reference) | 984 | 451 | 1 (reference) |
| CIMP-high | 130 | 109 | 1.06 (0.83–1.37) | 145 | 129 | 1.02 (0.81–1.29) |
| BRAF mutation status | ||||||
| BRAF wild-type | 1014 | 779 | 1 (reference) | 1116 | 916 | 1 (reference) |
| BRAF mutant | 110 | 90 | 1.66 (0.96–2.87) | 123 | 110 | 1.55 (1.22–1.97) |
| KRAS mutation status | ||||||
| KRAS wild-type | 606 | 482 | 1 (reference) | 673 | 567 | 1 (reference) |
| KRAS mutant | 381 | 298 | 1.01 (0.86–1.19) | 432 | 352 | 1.00 (0.87–1.16) |
a
Adjusted for sex, age, primary tumor location, disease stage, study (as strata), family history of colorectal cancer, year of diagnosis, MSI status, CIMP status, BRAF mutation, and KRAS mutation except for the predictor.
Abbreviations: CI, confidence interval; CIMP, CpG island methylator phenotype; CRC, colorectal cancer; HR, hazard ratio; MSI, microsatellite instability.