Table 3.
Association of MLH1 methylation1 in CIMP-positive2 CRC’s with overall survival3 after CRC diagnosis*
| Analysis | Unweighted N(deaths) |
Weighted N (deaths) |
HR (95% CI) |
|---|---|---|---|
| Overall Survival (baseline analysis4) | 390 (162) | ||
| MLH1 unmethylated | 188 (92) | 371 (168) | |
| MLH1 methylated | 202 (70) | 374 (118) | 0.50 (0.31, 0.82) |
| Additionally controlling for MSI status | 0.47 (0.20, 1.08) | ||
| Additionally controlling for BRAF5 mutation status | 0.49 (0.28, 0.86) | ||
| Additionally controlling for KRAS6 mutation status | 0.50 (0.28, 0.87) | ||
| Additionally controlling for joint BRAF and KRAS status | 0.51 (0.28–0.91) | ||
| In BRAF mutated cases | 250 (97) | 465 (179) | 0.41 (0.22, 0.77) |
| In BRAF wild-type cases | 136 (62) | 269 (103) | 0.88 (0.39–1.99) |
| Missing BRAF status | 4 (3) | ||
| In KRAS mutated cases | 64 (28) | 137 (52) | 1.35 (0.29, 6.33) |
| In KRAS wild-type cases | 265 (113) | 499 (193) | 0.46 (0.25, 0.84) |
| Missing KRAS status | 61 (21) | ||
| BRAF mutated/KRAS wildtype | 209 (87) | 392 (153) | 0.41 (0.21, 0.79) |
| BRAF wildtype/KRAS mutated | 63 (28) | 135 (52) | 3.60 (0.98, 13.23) |
| BRAF wildtype/KRAS wildtype | 55 (25) | 106 (39) | 0.35 (0.13, 0.91) |
Excludes 21 cases with missing information on date of diagnosis or death.
MLH1 methylation was defined as a PMR ≥ 10 using MethyLight analysis as defined in the text.
Defined as a PMR ≥10 for at least 3 of 5 genes: CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1.
Median follow-up from time since diagnosis was 10 years (range 5 months – 15 years). Overall survival was estimated using a Cox proportional hazards regression.
Baseline analysis adjusted for age, sex, tumor site (proximal vs. distal/rectal) and family history of CRC in at least one 1st degree relative (yes, no). Stratification factors were as identified in column one of the table.
Presence of the BRAF V600E mutation.
Presence of either a codon 12 or codon 13 KRAS mutation.