Table 4.
Multivariable-adjusted HRsa and 95%-CIs for associations between adiposity measures and CRC for individual mutations and MMR status, by sex and tumor location; NLCS, 1986–2006
| Person-years at risk | KRASmut | PIK3CAmutb | BRAFmutb | dMMRb | |||||
|---|---|---|---|---|---|---|---|---|---|
| ncases | HR (95% CI) | 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 | 61 | 1.00 (ref.) | 27 | 1.00 (ref.) | 25 | 1.00 (ref.) | 19 | 1.00 (ref.) |
| 23.4–24.9 (24.2) | 8343 | 58 | 0.89 (0.60–1.32) | 38 | 1.37 (0.81–2.30) | 28 | 1.11 (0.62–1.96) | 13 | 0.68 (0.33–1.42) |
| 25.0–26.6 (25.7) | 7683 | 69 | 1.12 (0.76–1.65) | 42 | 1.66 (0.98–2.81) | 29 | 1.22 (0.68–2.20) | 21 | 1.21 (0.63–2.34) |
| > 26.6 (27.8) | 7003 | 68 | 1.30 (0.88–1.92) | 43 | 1.97 (1.17–3.32) | 23 | 1.14 (0.61–2.14) | 17 | 1.17 (0.59–2.31) |
| p-trend | 0.112 | 0.007 | 0.603 | 0.378 | |||||
| per 5 kg/m2 | 31,022 | 256 | 1.25 (1.00–1.57) | 150 | 1.38 (1.05–1.82) | 105 | 1.23 (0.87–1.72) | 70 | 1.51 (1.01–2.26) |
| Men—rectum | |||||||||
| < 23.4 (22.2) | 7993 | 18 | 1.00 (ref.) | ||||||
| 23.4–24.9 (24.2) | 8343 | 13 | 0.67 (0.31–1.44) | ||||||
| 25.0–26.6 (25.7) | 7683 | 19 | 1.06 (0.53–2.15) | ||||||
| > 26.6 (27.8) | 7003 | 18 | 1.21 (0.59–2.47) | ||||||
| p-trend | 0.415 | ||||||||
| per 5 kg/m2 | 31,022 | 68 | 1.17 (0.79–1.73) | ||||||
| Women—colon | |||||||||
| < 22.8 (21.5) | 9014 | 52 | 1.00 (ref.) | 30 | 1.00 (ref.) | 53 | 1.00 (ref.) | 43 | 1.00 (ref.) |
| 22.8–24.7 (23.8) | 8914 | 46 | 0.88 (0.58–1.35) | 27 | 0.89 (0.52–1.53) | 40 | 0.76 (0.49–1.19) | 34 | 0.78 (0.49–1.26) |
| 24.8–27.0 (25.7) | 8141 | 65 | 1.48 (0.99–2.20) | 30 | 1.08 (0.64–1.84) | 39 | 0.82 (0.52–1.29) | 24 | 0.61 (0.36–1.03) |
| > 27.0 (29.2) | 8158 | 59 | 1.37 (0.90–2.08) | 29 | 1.01 (0.60–1.73) | 41 | 0.90 (0.57–1.41) | 30 | 0.78 (0.48–1.30) |
| p-trend | 0.031 | 0.798 | 0.678 | 0.221 | |||||
| per 5 kg/m2 | 34,228 | 222 | 1.31 (1.10–1.57)* | 116 | 1.09 (0.84–1.42) | 173 | 0.99 (0.81–1.22) | 131 | 0.90 (0.70–1.15) |
| Women—rectum | |||||||||
| < 22.8 (21.5) | 9014 | 18 | 1.00 (ref.) | ||||||
| 22.8–24.7 (23.8) | 8914 | 7 | 0.40 (0.17–0.98) | ||||||
| 24.8–27.0 (25.7) | 8141 | 9 | 0.57 (0.24–1.33) | ||||||
| > 27.0 (29.2) | 8158 | 21 | 1.46 (0.72–2.96) | ||||||
| p-trend | 0.312 | ||||||||
| per 5 kg/m2 | 34,228 | 55 | 1.21 (0.87–1.67) | ||||||
| Clothing size: range (median) | |||||||||
| Men—colon | |||||||||
| ≤ 50 (50) | 10,903 | 73 | 1.00 (ref.) | 40 | 1.00 (ref.) | 30 | 1.00 (ref.) | 18 | 1.00 (ref.) |
| 52 (52) | 9750 | 84 | 1.26 (0.89–1.78) | 52 | 1.45 (0.94–2.24) | 29 | 1.04 (0.61–1.78) | 23 | 1.37 (0.71–2.64) |
| 54 (54) | 5156 | 48 | 1.33 (0.88–2.02) | 22 | 1.20 (0.69–2.09) | 21 | 1.40 (0.77–2.55) | 12 | 1.37 (0.64–2.95) |
| ≥ 56 (56) | 2619 | 29 | 1.63 (1.00–2.65) | 17 | 1.80 (0.98–3.31) | 9 | 1.19 (0.54–2.61) | 7 | 1.55 (0.63–3.81) |
| p-trend | 0.040 | 0.094 | 0.360 | 0.280 | |||||
| per 2 sizes | 28,428 | 234 | 1.24 (1.01–1.54) | 131 | 1.31 (1.01–1.70) | 89 | 1.18 (0.85–1.64) | 60 | 1.33 (0.90–1.96) |
| Men—rectum | |||||||||
| ≤ 50 (50) | 10,903 | 21 | 1.00 (ref.) | ||||||
| 52 (52) | 9750 | 17 | 0.90 (0.45–1.77) | ||||||
| 54 (54) | 5156 | 17 | 1.71 (0.86–3.40) | ||||||
| ≥ 56 (56) | 2619 | 9 | 1.78 (0.78–4.06) | ||||||
| p-trend | 0.073 | ||||||||
| per 2 sizes | 28,428 | 64 | 1.17 (0.80–1.73) | ||||||
| Women—colon | |||||||||
| ≤ 40 (40) | 6574 | 35 | 1.00 (ref.) | 24 | 1.00 (ref.) | 29 | 1.00 (ref.) | 32 | 1.00 (ref.) |
| 42 (42) | 8582 | 54 | 1.13 (0.72–1.78) | 25 | 0.75 (0.42–1.34) | 47 | 1.23 (0.75–2.03) | 35 | 0.82 (0.49–1.37) |
| 44 (44) | 9270 | 58 | 1.10 (0.70–1.72) | 33 | 0.84 (0.48–1.45) | 45 | 1.02 (0.62–1.68) | 25 | 0.51 (0.29–0.88) |
| ≥ 46 (46) | 9454 | 70 | 1.33 (0.86–2.05) | 30 | 0.74 (0.42–1.30) | 49 | 1.11 (0.67–1.83) | 37 | 0.76 (0.45–1.28) |
| p-trend | 0.229 | 0.423 | 0.957 | 0.174 | |||||
| per 2 sizes | 33,880 | 217 | 1.26 (1.03–1.53) | 112 | 1.05 (0.82–1.35) | 170 | 1.04 (0.84–1.27) | 129 | 0.90 (0.71–1.14) |
| Women—rectum | |||||||||
| ≤ 40 (40) | 6574 | 10 | 1.00 (ref.) | ||||||
| 42 (42) | 8582 | 9 | 0.65 (0.26–1.62) | ||||||
| 44 (44) | 9270 | 12 | 0.76 (0.32–1.84) | ||||||
| ≥ 46 (46) | 9454 | 23 | 1.41 (0.63–3.13) | ||||||
| p-trend | 0.243 | ||||||||
| per 2 sizes | 33,880 | 54 | 1.07 (0.77–1.51) | ||||||
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
*Statistically significant p-heterogeneity, p = 0.008 (reference group: wild-type for KRAS, PIK3CA, and BRAF, and pMMR). Note: other p-heterogeneity tests were not statistically significant
aHazard Ratios were adjusted for age (years; continuous), non-occupational physical activity (minutes/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)
bAnalyses for subgroups with < 50 cases were not performed