Table 3.
Hazard ratio and 95% confidence interval of incident colorectal cancer, jointly classified by MSI and BRAF/CIMP status, according to intake of marine ω-3 polyunsaturated fatty acids in the Nurses’ Health Study (1984–2010) and Health Professionals Follow-up Study (1986–2010)*
| CIMP or BRAF mutation status of CRC | MSI status of CRC | <0.10g/d | 0.10–0.19g/d | 0.20–0.29g/d | ≥0.30g/d | P trend |
|---|---|---|---|---|---|---|
| CIMP-high | MSS CRC | |||||
| No. of cases (n = 58) | 8 | 15 | 13 | 22 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 0.93 (0.39 to 2.19) | 1.02 (0.42 to 2.47) | 1.41 (0.62 to 3.23) | .25 | |
| MSI-high CRC | ||||||
| No. of cases (n = 130) | 28 | 38 | 31 | 33 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 0.62 (0.38 to 1.01) | 0.69 (0.41 to 1.16) | 0.62 (0.37 to 1.04) | .23 | |
| P heterogeneity‡ | .42 | .46 | .09 | |||
| CIMP-low/negative | MSS CRC | |||||
| No. of cases (n = 818) | 121 | 268 | 183 | 246 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 1.08 (0.87 to 1.34) | 0.95 (0.75 to 1.21) | 0.93 (0.74 to 1.17) | .16 | |
| MSI-high CRC | ||||||
| No. of cases (n=45) | 14 | 13 | 9 | 9 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 0.43 (0.20 to 0.91) | 0.39 (0.17 to 0.91) | 0.28 (0.12 to 0.66) | .02 | |
| P heterogeneity‡ | .02 | .04 | .007 | |||
| BRAF-mutated | MSS CRC | |||||
| No. of cases (n = 64) | 8 | 20 | 17 | 19 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 1.24 (0.54 to 2.84) | 1.45 (0.62 to 3.40) | 1.37 (0.59 to 3.17) | .52 | |
| MSI-high CRC | ||||||
| No. of cases (n = 82) | 19 | 26 | 20 | 17 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 0.61 (0.34 to 1.11) | 0.64 (0.34 to 1.21) | 0.47 (0.24 to 0.93) | .06 | |
| P heterogeneity‡ | .17 | .13 | .05 | |||
| BRAF-wild-type | MSS CRC | |||||
| No. of cases (n = 815) | 121 | 262 | 181 | 251 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 1.05 (0.84 to 1.31) | 0.92 (0.73 to 1.17) | 0.90 (0.72 to 1.13) | .10 | |
| MSI-high CRC | ||||||
| No. of cases (n = 85) | 20 | 21 | 16 | 28 | ||
| Multivariable HR (95% CI)† | 1.00 (referent) | 0.48 (0.26 to 0.89) | 0.48 (0.25 to 0.93) | 0.60 (0.33 to 1.08) | .47 | |
| P heterogeneity‡ | .02 | .07 | .20 |
* All P values are two-sided. CI = confidence interval; CIMP = CpG island methylator phenotype; CRC = colorectal cancer; HR = hazard ratio; MSI = microsatellite instability; MSS = microsatellite stable.
† Adjusted for the same set of covariables as in Table 2.
‡Likelihood ratio test was used to compare the model that allows for separate associations for MSS and MSI-high tumors to the model that assumes a common association across subtypes.