Table 4.
The empirical dietary inflammatory pattern scores and risk of colorectal cancer according to microsatellite instability, PTGS2 (cyclooxygenase 2) and F nucleatum status in tumor tissues in the pooled cohorts of the Nurses’ Health Study (women, 1984–2012) and the Health Professionals Follow-up Study (men, 1986–2012)
| Molecular characteristic | Tumor F nucleatum status |
Tertiles of the empirical dietary inflammatory pattern (EDIP) scores | Ptrend* | |||
|---|---|---|---|---|---|---|
|
| ||||||
| T1 (lowest) | T2 | T3 (highest) | ||||
| Microsatellite instability (MSI) status | ||||||
| Non-MSI-high | N of cases (n=999) | 330 | 341 | 328 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.02 (0.88 – 1.19) | 1.05 (0.90 – 1.23) | 0.50 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.08 (0.92 – 1.26) | 1.12 (0.95 – 1.31) | 0.18 | ||
| Negative | N of cases (n=699) | 225 | 247 | 227 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.10 (0.92 – 1.32) | 1.07 (0.89 – 1.29) | 0.47 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.15 (0.95 – 1.38) | 1.12 (0.92 – 1.36) | 0.25 | ||
| Positive | N of cases (n=68) | 22 | 19 | 27 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 0.84 (0.45 – 1.56) | 1.37 (0.77 – 2.41) | 0.26 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 0.88 (0.47 – 1.63) | 1.44 (0.82 – 2.55) | 0.19 | ||
| MSI-high | N of cases (n=187) | 60 | 73 | 54 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.20 (0.85 – 1.69) | 0.97 (0.67 – 1.40) | 0.92 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.26 (0.89 – 1.78) | 1.01 (0.70 – 1.47) | 0.86 | ||
| Negative | N of cases (n=100) | 35 | 36 | 29 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.00 (0.63 – 1.60) | 0.87 (0.53 – 1.42) | 0.65 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.04 (0.65 – 1.67) | 0.90 (0.54 – 1.48) | 0.76 | ||
| Positive | N of cases (n=43) | 9 | 18 | 16 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 2.01 (0.90 – 4.49) | 1.95 (0.86 – 4.43) | 0.11 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 2.10 (0.94 – 4.70) | 2.01 (0.88 – 4.56) | 0.09 | ||
|
| ||||||
| PTGS2 expression status | ||||||
| Negative | N of cases (n=432) | 148 | 154 | 130 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.00 (0.80 – 1.26) | 0.92 (0.73 – 1.17) | 0.53 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.05 (0.84 – 1.33) | 0.97 (0.76 – 1.24) | 0.84 | ||
| Negative | N of cases (n=277) | 96 | 99 | 82 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.00 (0.76 – 1.33) | 0.90 (0.67 – 1.21) | 0.53 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.05 (0.79 – 1.40) | 0.93 (0.69 – 1.26) | 0.72 | ||
| Positive | N of cases (n=43) | 11 | 16 | 16 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.42 (0.65 – 3.07) | 1.55 (0.71 – 3.35) | 0.29 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.47 (0.68 – 3.21) | 1.59 (0.73 – 3.44) | 0.26 | ||
| Positive | N of cases (n=692) | 223 | 239 | 230 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.06 (0.89 – 1.28) | 1.10 (0.91 – 1.32) | 0.37 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.12 (0.93 – 1.34) | 1.15 (0.95 – 1.39) | 0.18 | ||
| Negative | N of cases (n=444) | 145 | 155 | 144 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.07 (0.85 – 1.34) | 1.05 (0.83 – 1.32) | 0.73 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.11 (0.88 – 1.40) | 1.08 (0.85 – 1.37) | 0.56 | ||
| Positive | N of cases (n=51) | 12 | 17 | 22 | ||
| Age-adjusted HR (95% CI) | 1 (reference) | 1.41 (0.67 – 2.97) | 2.15 (1.06 – 4.36) | 0.03 | ||
| Multivariable HR (95% CI)† | 1 (reference) | 1.47 (0.70 – 3.10) | 2.22 (1.09 – 4.51) | 0.02 | ||
CI, confidence interval; F nucleatum, Fusobacterium nucleatum; HR, hazard ratio; MSI, microsatellite instability; T1, tertile 1; T2, tertile 2; T3, tertile 3.
Cox proportional cause-specific hazards regression for competing risks data was used to compute HRs and 95% CIs.
All analyses were stratified by age (in month), year of questionnaire return and sex.
Linear trend test using the median value of each category.
Multivariable HR was adjusted for pack-years smoked (0 vs 1–19 vs 20–39 vs ≥ 40 pack-years), family history of colorectal cancer (yes vs no), endoscopy status (yes vs no), physical activity level [quintiles of mean metabolic equivalent task score (METS) - hours per week], total calorie intake (quintiles of kcal/day), total alcohol intake (0 vs 1–5 vs 6–15 vs > 15 g/day), current multivitamin use (yes vs no), and regular aspirin use (yes vs no).