Table 3. Associations of CIMP in combination with microsatellite instability, BRAF mutation and KRAS mutation with survival among CRC patients.

		Overall survivala			Disease-specific survivala
Factor	N	Deaths (%)	HR	95% CI	Deaths (%)	HR	95% CI
CIMP-L/N and MSS	1113	320 (29)	1.00	Reference	250 (22)	1.00	Reference
CIMP-H and MSS	108	35 (32)	1.02	0.71–1.46	26 (24)	0.92	0.61–1.40
CIMP-L/N and MSI-H	57	10 (18)	0.80	0.42–1.53	4 (7)	0.42	0.15–1.14
CIMP-H and MSI-H	79	17 (22)	0.75	0.43–1.32	9 (11)	0.54	0.26–1.12
Any CIMP and MSI-H	136	27 (20)	0.77	0.49–1.21	13 (10)	0.49	0.27–0.90
CIMP-L/N and BRAF−	1125	313 (28)	1.00	Reference	239 (21)	1.00	Reference
CIMP-H and BRAF−	133	40 (30)	1.08	0.77–1.53	25 (19)	0.96	0.62–1.46
CIMP-L/N and BRAF+	45	17 (38)	1.50	0.90–2.49	15 (33)	1.80	1.04–3.11
CIMP-H and BRAF+	54	12 (22)	0.99	0.51–1.94	10 (19)	1.73	0.82–3.66
Any CIMP and BRAF+	99	29 (29)	1.28	0.82–1.98	25 (25)	1.78	1.10–2.84
CIMP-L/N and KRAS−	712	191 (27)	1.00	Reference	147 (21)	1.00	Reference
CIMP-H and KRAS−	128	41 (32)	1.08	0.73–1.59	28 (22)	0.99	0.62–1.56
CIMP-L/N and KRAS+	346	106 (31)	1.12	0.88–1.43	82 (24)	1.08	0.82–1.43
CIMP-H and KRAS+	50	9 (18)	0.81	0.41–1.43	5 (10)	0.61	0.24–1.53
Any CIMP and KRAS+	396	115 (29)	1.09	0.86–1.38	87 (22)	1.04	0.79–1.36

Abbreviations: BRAF+=BRAF mutation; BRAF−=BRAF wild type; CI=confidence interval; CIMP=CpG island methylator phenotype; CIMP-H=CIMP-high; CIMP-L/N=CIMP-low/negative; CRC=colorectal cancer; HR=hazard ratio; KRAS+=KRAS mutation; KRAS−=KRAS wild type; MSI-H=microsatellite instability-high; MSS=microsatellite stability.

^aAdjusted for age, sex, education level, alcohol consumption, tumour location, cancer stage, number of invaded lymph nodes, usage of hormone replacement therapy, chemotherapy, microsatellite instability and BRAF mutation; additional adjustment for time-dependent effects of age and chemotherapy.