Table 5.
Multivariable-adjusteda HRs and 95% CI for the relation between nut and peanut butter intake and the risk of CRC developed through the traditional adenoma-carcinoma pathway (truncating APC mutation and/or activating KRAS mutation and/or p53 overexpression) and the serrated neoplasia pathway (BRAF mutation and/or MSI); NLCS, 1986–1993, excluding the first 2.3 years of follow-up
| Subcohort | Traditional pathway | No traditional pathway | Serrated pathway | No serrated pathway | |||||
|---|---|---|---|---|---|---|---|---|---|
| Person-years | N cases | HR (95% CI) | N cases | HR (95% CI) | N cases | HR (95% CI) | N cases | HR (95% CI) | |
| Men | |||||||||
| Total nuts (g/day) | |||||||||
| 0.0 | 2592 | 95 | 1 (reference) | 19 | 1 (reference) | 19 | 1 (reference) | 81 | 1 (reference) |
| 0.1–<5 | 2767 | 81 | 0.87 (0.63–1.22) | 21 | 1.24 (0.66–2.32) | 22 | 1.25 (0.64–2.45) | 67 | 0.87 (0.61–1.25) |
| 5+ | 3129 | 77 | 0.73 (0.51–1.03) | 16 | 0.81 (0.39–1.67) | 18 | 0.88 (0.43–1.80) | 65 | 0.72 (0.49–1.05) |
| P-trend | 0.086 | 0.387 | 0.502 | 0.104 | |||||
| FDR-adjusted P-trendb | 0.458 | 0.688 | 0.730 | 0.458 | |||||
| Per 5 g/day increment | 0.97 (0.91–1.04) | 0.98 (0.87–1.11) | 0.96 (0.86–1.08) | 0.96 (0.89–1.04) | |||||
| P-heterogeneity | 0.729 | 0.652 | |||||||
| Tree nuts (g/day) | |||||||||
| 0.0 | 6175 | 195 | 1 (reference) | 42 | 1 (reference) | 40 | 1 (reference) | 167 | 1 (reference) |
| 0.1+ | 2314 | 58 | 0.82 (0.60–1.13) | 14 | 0.98 (0.51–1.89) | 19 | 1.31 (0.76–2.25) | 46 | 0.76 (0.53–1.09) |
| P-trend | 0.230 | 0.960 | 0.336 | 0.136 | |||||
| FDR-adjusted P-trendb | 0.613 | 0.983 | 0.688 | 0.458 | |||||
| Per 5 g/day increment | 0.93 (0.72–1.20) | 0.85 (0.47–1.53) | 1.09 (0.82–1.46) | 0.89 (0.66–1.21) | |||||
| P-heterogeneity | 0.745 | 0.093 | |||||||
| Peanuts (g/day) | |||||||||
| 0.0 | 2913 | 103 | 1 (reference) | 20 | 1 (reference) | 20 | 1 (reference) | 88 | 1 (reference) |
| 0.1–<5/0.1+ | 3001/5576 | 90 | 0.95 (0.69–1.31) | 23 | 1.39 (0.76–2.57) | 26 | 1.49 (0.78–2.86) | 73 | 0.92 (0.65–1.30) |
| 5+ | 2575 | 60 | 0.73 (0.50–1.06) | 13 | 0.87 (0.41–1.85) | 13 | 0.83 (0.39–1.79) | 52 | 0.74 (0.50–1.11) |
| P-trend | 0.082 | 0.484 | 0.348 | 0.143 | |||||
| FDR-adjusted P-trendb | 0.458 | 0.730 | 0.688 | 0.458 | |||||
| Per 5 g/day increment | 0.97 (0.91–1.05) | 0.99 (0.88–1.12) | 0.95 (0.83–1.08) | 0.97 (0.89–1.05) | |||||
| P-heterogeneity | 0.732 | 0.383 | |||||||
| Peanut butter (g/day) | |||||||||
| 0.0 | 6082 | 185 | 1 (reference) | 40 | 1 (reference) | 42 | 1 (reference) | 158 | 1 (reference) |
| 0.1+ | 2407 | 68 | 1.02 (0.75–1.38) | 16 | 1.15 (0.61–2.18) | 17 | 1.07 (0.60–1.90) | 55 | 1.00 (0.71–1.40) |
| P-trend | 0.913 | 0.661 | 0.820 | 0.983 | |||||
| FDR-adjusted P-trendb | 0.983 | 0.881 | 0.983 | 0.983 | |||||
| Per 5 g/day increment | 1.18 (1.04–1.33) | 0.85 (0.57–1.26) | 0.93 (0.67–1.27) | 1.22 (1.07–1.38)* | |||||
| P-heterogeneity | 0.805 | 0.654 | |||||||
| Women | |||||||||
| Total nuts (g/day) | |||||||||
| 0.0 | 3641 | 86 | 1 (reference) | 24 | 1 (reference) | 23 | 1 (reference) | 78 | 1 (reference) |
| 0.1–<5 | 3295 | 76 | 1.05 (0.75–1.47) | 28 | 1.55 (0.87–2.78) | 28 | 1.55 (0.87–2.78) | 70 | 1.09 (0.77–1.56) |
| 5+ | 2149 | 34 | 0.76 (0.48–1.18) | 14 | 1.31 (0.63–2.73) | 12 | 1.03 (0.49–2.16) | 31 | 0.82 (0.51–1.31) |
| P-trend | 0.173 | 0.647 | 0.790 | 0.326 | |||||
| FDR-adjusted P-trendb | 0.752 | 0.846 | 0.903 | 0.846 | |||||
| Per 5 g/day increment | 0.98 (0.85–1.13) | 0.93 (0.77–1.12) | 0.95 (0.79–1.15) | 0.98 (0.84–1.15) | |||||
| P-heterogeneity | 0.558 | 0.600 | |||||||
| Tree nuts (g/day) | |||||||||
| 0.0 | 6378 | 149 | 1 (reference) | 45 | 1 (reference) | 44 | 1 (reference) | 132 | 1 (reference) |
| 0.1+ | 2706 | 47 | 0.78 (0.54–1.13) | 21 | 1.30 (0.73–2.29) | 19 | 1.13 (0.62–2.05) | 47 | 0.92 (0.63–1.33) |
| P-trend | 0.188 | 0.374 | 0.687 | 0.651 | |||||
| FDR-adjusted P-trendb | 0.752 | 0.846 | 0.846 | 0.846 | |||||
| Per 5 g/day increment | 0.98 (0.76–1.27) | 0.79 (0.45–1.40) | 0.70 (0.30–1.68) | 1.04 (0.87–1.24) | |||||
| P-heterogeneity | 0.222 | 0.563 | |||||||
| Peanuts (g/day) | |||||||||
| 0.0 | 4287 | 97 | 1 (reference) | 28 | 1 (reference) | 27 | 1 (reference) | 89 | 1 (reference) |
| 0.1–<5/0.1+ | 3360/4797 | 99 | 1.02 (0.74–1.40) | 38 | 1.53 (0.89–2.63) | 26 | 1.49 (0.82–2.69) | 71 | 1.14 (0.81–1.61) |
| 5+ | 1437 | 10 | 1.34 (0.63–2.87) | 19 | 0.77 (0.45–1.32) | ||||
| P-trend | 0.914 | 0.126 | 0.506 | 0.310 | |||||
| FDR-adjusted P-trendb | 0.975 | 0.752 | 0.846 | 0.846 | |||||
| Per 5 g/day increment | 0.98 (0.85–1.14) | 0.95 (0.78–1.16) | 0.99 (0.84–1.16) | 0.97 (0.80–1.16) | |||||
| P-heterogeneity | 0.300 | 0.494 | |||||||
| Peanut butter (g/day) | |||||||||
| 0.0 | 6643 | 149 | 1 (reference) | 45 | 1 (reference) | 47 | 1 (reference) | 134 | 1 (reference) |
| 0.1+ | 2441 | 47 | 0.92 (0.64–1.32) | 21 | 1.62 (0.93–2.81) | 16 | 1.16 (0.63–2.14) | 45 | 1.00 (0.69–1.45) |
| P-trend | 0.655 | 0.087 | 0.623 | 0.990 | |||||
| FDR-adjusted P-trendb | 0.846 | 0.752 | 0.846 | 0.990 | |||||
| Per 5 g/day increment | 0.82 (0.61–1.10) | 1.17 (0.83–1.64) | 1.03 (0.62–1.70) | 0.84 (0.63–1.13) | |||||
| P-heterogeneity | 0.222 | 0.969 |
aAdjusted for age (years; continuous), cigarette smoking [status (never/former/current), frequency (n/day; continuous, centered) and duration (years; continuous, centered)], BMI (kg/m2; continuous), non-occupational physical activity (≤30/>30–≤60/>60–≤90/>90 min/day), educational level (low/medium/high), family history of CRC (no/yes), total energy intake (kcal/day; continuous) and alcohol consumption (g/day; continuous).
bFDR-adjusted P-trends are calculated with adjustment for 16 tests per sex.
*P < 0.05 after FDR correction.