Table 3.
Multivariable-adjusted HRsa and 95%-CIs for associations between adiposity measures and CRC in subgroups based on mutation and MMR status, by sex and tumor location; NLCS, 1986–2006
| Person-years at risk | Total | Wild-type + pMMRb | Any-mutation/dMMRc | p-het | ||||
|---|---|---|---|---|---|---|---|---|
| ncases | HR (95% CI) | ncases | HR (95% CI) | ncases | HR (95% CI) | |||
| BMI quartiles (kg/m2): range (median) | ||||||||
| Men—colon | ||||||||
| < 23.4 (22.2) | 7993 | 167 | 1.00 (ref.) | 66 | 1.00 (ref.) | 101 | 1.00 (ref.) | |
| 23.4–24.9 (24.2) | 8343 | 188 | 1.06 (0.82–1.37) | 79 | 1.10 (0.76–1.57) | 109 | 1.04 (0.77–1.42) | |
| 25.0–26.6 (25.7) | 7683 | 200 | 1.21 (0.93–1.56) | 77 | 1.13 (0.78–1.64) | 123 | 1.26 (0.92–1.72) | |
| > 26.6 (27.8) | 7003 | 199 | 1.41 (1.09–1.83) | 87 | 1.47 (1.03–2.11) | 112 | 1.37 (0.99–1.88) | 0.710 |
| p-trend | 0.005 | 0.038 | 0.027 | |||||
| per 5 kg/m2 | 31,022 | 754 | 1.30 (1.12–1.51) | 309 | 1.34 (1.08–1.67) | 445 | 1.28 (1.07–1.53) | 0.454 |
| Men—rectum | ||||||||
| < 23.4 (22.2) | 7993 | 58 | 1.00 (ref.) | 34 | 1.00 (ref.) | 24 | 1.00 (ref.) | |
| 23.4–24.9 (24.2) | 8343 | 54 | 0.86 (0.57–1.28) | 35 | 0.95 (0.58–1.57) | 19 | 0.73 (0.39–1.37) | |
| 25.0–26.6 (25.7) | 7683 | 65 | 1.15 (0.78–1.69) | 42 | 1.29 (0.80–2.09) | 23 | 0.95 (0.51–1.74) | |
| > 26.6 (27.8) | 7003 | 47 | 0.93 (0.61–1.43) | 24 | 0.82 (0.47–1.44) | 23 | 1.09 (0.59–2.01) | 0.458 |
| p-trend | 0.851 | 0.870 | 0.636 | |||||
| per 5 kg/m2 | 31,022 | 224 | 1.02 (0.81–1.28) | 135 | 0.95 (0.71–1.26) | 89 | 1.14 (0.80–1.62) | 0.387 |
| Women—colon | ||||||||
| < 22.8 (21.5) | 9014 | 181 | 1.00 (ref.) | 56 | 1.00 (ref.) | 125 | 1.00 (ref.) | |
| 22.8–24.7 (23.8) | 8914 | 146 | 0.81 (0.63–1.05) | 43 | 0.78 (0.51–1.19) | 103 | 0.83 (0.62–1.11) | |
| 24.8–27.0 (25.7) | 8141 | 147 | 0.92 (0.71–1.20) | 36 | 0.73 (0.47–1.16) | 111 | 1.01 (0.75–1.36) | |
| > 27.0 (29.2) | 8158 | 156 | 1.01 (0.77–1.31) | 44 | 0.91 (0.59–1.41) | 112 | 1.05 (0.78–1.43) | 0.601 |
| p-trend | 0.805 | 0.595 | 0.516 | |||||
| per 5 kg/m2 | 34,228 | 630 | 1.04 (0.92–1.18) | 179 | 0.88 (0.69–1.11) | 451 | 1.11 (0.96–1.27) | 0.081 |
| Women—rectum | ||||||||
| < 22.8 (21.5) | 9014 | 37 | 1.00 (ref.) | 16 | 1.00 (ref.) | 21 | 1.00 (ref.) | |
| 22.8–24.7 (23.8) | 8914 | 26 | 0.69 (0.41–1.17) | 15 | 0.90 (0.43–1.89) | 11 | 0.53 (0.25–1.13) | |
| 24.8–27.0 (25.7) | 8141 | 32 | 0.91 (0.55–1.53) | 18 | 1.16 (0.58–2.34) | 14 | 0.75 (0.36–1.56) | |
| > 27.0 (29.2) | 8158 | 36 | 1.04 (0.63–1.72) | 15 | 0.93 (0.45–1.90) | 21 | 1.20 (0.61–2.38) | 0.491 |
| p-trend | 0.691 | 0.973 | 0.548 | |||||
| per 5 kg/m2 | 34,228 | 131 | 1.08 (0.86–1.34) | 64 | 1.05 (0.77–1.42) | 67 | 1.12 (0.82–1.53) | 0.872 |
| Clothing size: range (median) | ||||||||
| Men—colon | ||||||||
| ≤ 50 (50) | 10,903 | 211 | 1.00 (ref.) | 90 | 1.00 (ref.) | 121 | 1.00 (ref.) | |
| 52 (52) | 9750 | 247 | 1.30 (1.03–1.62) | 104 | 1.29 (0.94–1.77) | 143 | 1.30 (0.98–1.71) | |
| 54 (54) | 5156 | 136 | 1.36 (1.04–1.77) | 53 | 1.26 (0.86–1.84) | 83 | 1.43 (1.03–1.98) | |
| ≥ 56 (56) | 2619 | 90 | 1.80 (1.31–2.46) | 39 | 1.87 (1.22–2.86) | 51 | 1.75 (1.19–2.57) | 0.897 |
| p-trend | < 0.001 | 0.008 | 0.002 | |||||
| per 2 sizes | 28,428 | 684 | 1.33 (1.16–1.52) | 286 | 1.34 (1.12–1.61) | 398 | 1.32 (1.11–1.55) | 0.983 |
| Men—rectum | ||||||||
| ≤ 50 (50) | 10,903 | 78 | 1.00 (ref.) | 46 | 1.00 (ref.) | 32 | 1.00 (ref.) | |
| 52 (52) | 9750 | 69 | 1.00 (0.70–1.41) | 46 | 1.12 (0.73–1.72) | 23 | 0.80 (0.46–1.42) | |
| 54 (54) | 5156 | 43 | 1.20 (0.80–1.80) | 28 | 1.17 (0.70–1.96) | 18 | 1.23 (0.67–2.25) | |
| ≥ 56 (56) | 2619 | 16 | 0.90 (0.51–1.59) | 7 | 0.67 (0.29–1.51) | 9 | 1.23 (0.57–2.66) | 0.454 |
| p-trend | 0.801 | 0.760 | 0.470 | |||||
| per 2 sizes | 28,428 | 206 | 0.98 (0.81–1.20) | 124 | 0.95 (0.75–1.21) | 82 | 1.02 (0.74–1.41) | 0.711 |
| Women—colon | ||||||||
| ≤ 40 (40) | 6574 | 128 | 1.00 (ref.) | 46 | 1.00 (ref.) | 82 | 1.00 (ref.) | |
| 42 (42) | 8582 | 150 | 0.88 (0.67–1.17) | 34 | 0.58 (0.36–0.93) | 116 | 1.05 (0.76–1.46) | |
| 44 (44) | 9270 | 159 | 0.83 (0.63–1.10) | 48 | 0.74 (0.48–1.15) | 111 | 0.89 (0.64–1.23) | |
| ≥ 46 (46) | 9454 | 182 | 0.95 (0.72–1.26) | 50 | 0.78 (0.50–1.20) | 132 | 1.06 (0.77–1.46) | 0.104 |
| p-trend | 0.764 | 0.537 | 0.979 | |||||
| per 2 sizes | 33,880 | 619 | 1.08 (0.95–1.24) | 178 | 1.07 (0.82–1.40) | 441 | 1.09 (0.94–1.26) | 0.759 |
| Women—rectum | ||||||||
| ≤ 40 (40) | 6574 | 23 | 1.00 (ref.) | 11 | 1.00 (ref.) | 12 | 1.00 (ref.) | |
| 42 (42) | 8582 | 30 | 0.94 (0.53–1.67) | 17 | 1.13 (0.52–2.49) | 13 | 0.77 (0.34–1.73) | |
| 44 (44) | 9270 | 35 | 1.01 (0.58–1.75) | 20 | 1.28 (0.62–2.65) | 15 | 0.79 (0.35–1.77) | |
| ≥ 46 (46) | 9454 | 42 | 1.14 (0.66–1.97) | 16 | 0.96 (0.44–2.08) | 26 | 1.31 (0.62–2.78) | 0.319 |
| p-trend | 0.532 | 0.941 | 0.355 | |||||
| per 2 sizes | 33,880 | 130 | 0.99 (0.80–1.23) | 64 | 0.96 (0.71–1.28) | 66 | 1.02 (0.76–1.39) | 0.562 |
HR hazard ratio; CI confidence interval; CRC colorectal cancer; (d/p)MMR mismatch repair (deficient/proficient); NLCS Netherlands Cohort Study; BMI body mass index; p-het p-heterogeneity
aHazard ratios were adjusted for age (years; continuous), non-occupational physical activity (min/day; continuous), total energy intake (kcal/day; continuous), family history of CRC (yes/no), alcohol consumption (0; 0.1–4; 5–14; > 15 g/day), processed meat intake (g/day; continuous), red meat intake (g/day; continuous). Age was included as a time-varying covariate. BMI models were additionally adjusted for height (cm; continuous)
bThis group excludes cases with mutations in any of the genes (KRAS, PIK3CA, or BRAF), as well as MMR deficient cases
cThis group includes cases with mutations in any of the genes (KRAS, PIK3CA, or BRAF) and/or cases that are MMR deficient