Background
Methods
Study design and data source
Case ascertainment
Study population
Baseline data collection
Model development
Elastic net selection
Absolute risk assessment
Model performance: discrimination and calibration
Model discrimination
Model calibration
Model communication
Random survival forest
Sensitivity analyses
Results
Baseline characteristics
Characteristics | Derivation cohort | Validation cohort | ||||
---|---|---|---|---|---|---|
All participants | Men | Women | All participants | Men | Women | |
N | 255,482 | 83,101 | 172,381 | 74,403 | 29,259 | 45,144 |
Age at recruitment, years, mean (SD) | 51.4 (9.7) | 52.3 (9.0) | 51.0 (9.9) | 49.7 (9.6) | 50.7 (9.3) | 49.0 (9.8) |
Age range, years | 19.5 to 70.0 | 19.5 to 70.0 | 20.0 to 70.0 | 19.9 to 70.0 | 20.1 to 69.2 | 19.9 to 70.0 |
BMI, kg/m2, mean (SD) | 25.8 (4.3) | 26.6 (3.6) | 25.4 (4.5) | 26.0 (4.2) | 26.6 (3.6) | 25.7 (4.5) |
Waist, cm, mean (SD) | 84.6 (12.9) | 94.6 (10.0) | 79.8 (11.3) | 86.0 (12.5) | 94.0 (10.2) | 80.8 (11.0) |
Height, cm, mean (SD) | 165.8 (9.1) | 174.3 (7.3) | 161.7 (6.7) | 167.3 (9.6) | 175.5 (7.3) | 162.1 (6.9) |
Postmenopausal status, % | 49.5 | 41.8 | ||||
Ever use of hormone for menopause, % | 26.0 | 23.8 | ||||
Smoking status, % | ||||||
Smoker | 23.5 | 31.3 | 19.7 | 27.0 | 32.3 | 23.5 |
Former | 27.4 | 36.2 | 23.1 | 27.8 | 37.3 | 21.6 |
Never | 49.1 | 32.4 | 57.2 | 45.3 | 30.4 | 54.9 |
Physical activity, % | ||||||
Inactive | 19.1 | 29.4 | 14.2 | 18.3 | 25.3 | 13.7 |
Moderately inactive | 30.3 | 32.9 | 29.0 | 27.2 | 30.0 | 25.4 |
Moderately active | 40.2 | 29.3 | 45.5 | 43.5 | 33.7 | 49.9 |
Active | 10.3 | 8.5 | 11.2 | 11.0 | 11.0 | 11.0 |
Education, % | ||||||
None | 5.9 | 4.9 | 6.3 | 3.1 | 2.4 | 3.6 |
Primary school completed | 27.0 | 30.6 | 25.2 | 29.2 | 24.8 | 32.1 |
Technical school/professional school | 22.4 | 22.7 | 22.3 | 31.1 | 29.8 | 31.9 |
Secondary school | 16.2 | 11.9 | 18.3 | 13.4 | 11.4 | 14.7 |
University degree | 24.6 | 27.4 | 23.3 | 23.0 | 31.5 | 17.5 |
Not specified | 4.0 | 2.5 | 4.7 | 0.2 | 0.2 | 0.3 |
Dietary intake, g/day, median (IQR) | ||||||
Alcohol | 6.6 (1.1 to 17.1) | 14.4 (5.0 to 32.3) | 4.1 (0.6 to 11.9) | 7.8 (1.5 to 19.7) | 16.4 (6.7 to 32.9) | 4.2 (0.6 to 11.8) |
Vegetables | 196.9 (124.4 to 301.8) | 179.7 (110.8 to 287.8) | 204.9 (131.5 to 307.4) | 130.0 (92.8 to 183.2) | 124.0 (88.1 to 174.7) | 133.9 (95.9 to 189.1) |
Fruits | 215.1 (117.1 to 340.8) | 176.6 (88.5 to 313.3) | 232.7 (132.4 to 351.8) | 161.0 (94.1 to 264.7) | 127.4 (73.9 to 225.3) | 186.0 (105.6 to 290.3) |
Dark bread | 28.6 (0.0 to 91.8) | 34.9 (0.0 to 112.5) | 27.9 (0.0 to 87.8) | 91.4 (15.0 to 150.2) | 115.8 (49.3 to 179.6) | 73.2 (8.0 to 128.0) |
Dairy products | 283.0 (159.5 to 447.5) | 257.3 (130.0 to 434.3) | 295.2 (173.1 to 451.7) | 265.1 (150.0 to 434.7) | 256.8 (136.7 to 447.0) | 270.2 (158.8 to 428.7) |
Red meat | 38.2 (17.3 to 65.4) | 49.7 (24.8 to 80.5) | 33.8 (13.9 to 57.3) | 44.8 (23.9 to 74.5) | 61.9 (33.5 to 93.1) | 36.9 (19.8 to 61.1) |
Poultry | 16.1 (5.8 to 30.9) | 16.4 (7.3 to 34.3) | 15.8 (4.8 to 29.3) | 13.2 (6.5 to 24.3) | 14.6 (7.3 to 25.5) | 12.4 (5.9 to 23.4) |
Processed meat | 19.2 (6.4 to 37.9) | 27.9 (10.8 to 51.9) | 16.4 (5.4 to 31.8) | 34.5 (17.9 to 59.6) | 47.6 (27.4 to 76.7) | 27.8 (14.6 to 48.7) |
Fish | 21.4 (9.3 to 37.0) | 24.3 (12.6 to 41.2) | 19.7 (7.7 to 34.9) | 16.1 (6.0 to 30.3) | 17.6 (6.3 to 32.2) | 15.3 (5.9 to 27.9) |
Sugar and confectionary | 31.6 (16.3 to 55.2) | 36.9 (19.2 to 65.0) | 29.6 (15.2 to 51.0) | 35.3 (18.7 to 60.0) | 41.0 (21.7 to 70.3) | 32.3 (17.1 to 54.1) |
Soft drinks | 9.5 (0.0 to 85.7) | 16.4 (0.0 to 100.0) | 6.6 (0.0 to 74.3) | 8.7 (0.0 to 85.7) | 19.3 (0.0 to 118.7) | 3.8 (0.0 to 66.0) |
Model development
Predictor variables | Hazard ratios (95% confidence intervals), p value | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Both sexes | Men | Women | ||||||||||
Full model* | Reduced model† (LiFeCRC score) | Full model* | Reduced model† | Full model* | Reduced model† | |||||||
Age at recruitment, per 10 years | 2.23 (2.13 to 2.33) | < .001 | 2.18 (2.09 to 2.29) | < .001 | 2.19 (2.04 to 2.35) | < .001 | 2.12 (1.98 to 2.27) | < .001 | 2.26 (2.13 to 2.40) | < .001 | 2.21 (2.08 to 2.34) | < .001 |
Waist circumference, per 10 cm | 1.12 (1.09 to 1.15) | < .001 | 1.12 (1.09 to 1.16) | < .001 | 1.19 (1.13 to 1.25) | < .001 | 1.19 (1.13 to 1.25) | < .001 | 1.06 (1.01 to 1.10) | 0.008 | 1.05 (1.01 to 1.09) | 0.023 |
Height, per 10 cm | 1.13 (1.08 to 1.17) | < .001 | 1.12 (1.08 to 1.17) | < .001 | 1.04 (0.96 to 1.11) | 0.333 | 1.14 (1.06 to 1.22) | < .001 | 1.16 (1.08 to 1.24) | < .001 | ||
Daily alcohol consumption, high | 1.14 (1.06 to 1.23) | < .001 | 1.14 (1.06 to 1.22) | < .001 | 1.18 (1.07 to 1.31) | 0.002 | 1.18 (1.06 to 1.30) | 0.002 | 1.06 (0.96 to 1.18) | 0.245 | ||
Ever smoker, yes | 1.24 (1.16 to 1.33) | < .001 | 1.24 (1.15 to 1.32) | < .001 | 1.31 (1.17 to 1.47) | < .001 | 1.31 (1.17 to 1.46) | < .001 | 1.15 (1.05 to 1.26) | 0.003 | 1.16 (1.06 to 1.27) | 0.001 |
Physically active, yes | 0.89 (0.82 to 0.97) | 0.010 | 0.91 (0.83 to 0.99) | 0.026 | 0.93 (0.83 to 1.04) | 0.185 | 0.87 (0.76 to 0.99) | 0.029 | ||||
Vegetables, per 100 g/day | 0.92 (0.90 to 0.95) | < .001 | 0.93 (0.90 to 0.95) | < .001 | 0.89 (0.85 to 0.93) | < .001 | 0.89 (0.85 to 0.92) | < .001 | 0.95 (0.92 to 0.99) | 0.009 | 0.93 (0.90 to 0.97) | < .001 |
Fruits, per 100 g/day | 0.99 (0.97 to 1.01) | 0.180 | 0.99 (0.96 to 1.02) | 0.424 | 0.98 (0.96 to 1.01) | 0.196 | ||||||
Dark bread, per 50 g/day | 0.98 (0.96 to 1.01) | 0.147 | 0.96 (0.93 to 0.99) | 0.015 | 0.97 (0.94 to 1.00) | 0.070 | 1.02 (0.98 to 1.06) | 0.329 | ||||
Dairy products, per 100 g/day | 0.98 (0.97 to 0.99) | 0.006 | 0.98 (0.97 to 1.00) | 0.017 | 0.98 (0.96 to 1.00) | 0.016 | 0.98 (0.96 to 1.00) | 0.048 | 0.99 (0.97 to 1.01) | 0.198 | ||
Red meat, per 50 g/day | 1.03 (0.99 to 1.08) | 0.158 | 1.06 (1.00 to 1.13) | 0.046 | 1.08 (1.02 to 1.14) | 0.010 | 0.98 (0.91 to 1.06) | 0.577 | ||||
Poultry, per 50 g/day | 1.03 (0.95 to 1.12) | 0.461 | 1.07 (0.96 to 1.20) | 0.210 | 0.99 (0.87 to 1.12) | 0.845 | ||||||
Processed meat, per 50 g/day | 1.08 (1.02 to 1.14) | 0.006 | 1.08 (1.03 to 1.14) | 0.004 | 1.04 (0.97 to 1.11) | 0.296 | 1.13 (1.03 to 1.24) | 0.010 | 1.12 (1.02 to 1.23) | 0.020 | ||
Fish, per 50 g/day | 0.99 (0.93 to 1.05) | 0.665 | 1.00 (0.93 to 1.09) | 0.914 | 0.92 (0.83 to 1.02) | 0.109 | ||||||
Sugar and confectionary, per 50 g/day | 1.03 (1.00 to 1.05) | 0.028 | 1.03 (1.00 to 1.05) | 0.022 | 1.02 (0.99 to 1.05) | 0.118 | 1.04 (0.99 to 1.09) | 0.088 | ||||
Soft drinks, per 100 g/day | 1.02 (1.00 to 1.03) | 0.097 | 1.01 (0.99 to 1.04) | 0.392 | 1.02 (1.00 to 1.05) | 0.095 | ||||||
Survival functionm (10 years)‡ | 0.9944 | 0.9943 | 0.9920 | 0.9919 | 0.9953 | 0.9952 | ||||||
Risk Scorem§ | 6.8953 | 6.8089 | 6.2600 | 5.5356 | 6.4758 | 6.7039 | ||||||
Absolute Riskm (10 years)# | 0.78% | 0.78% | 1.07% | 1.07% | 0.64% | 0.64% |
Predictor variables | Hazard ratios (95% confidence intervals), p-value | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Colon cancer | Rectal cancer | |||||||||||
Both sexes | Men | Women | Both sexes | Men | Women | |||||||
Age at recruitment, per 10 years | 2.30 (2.17 to 2.44) | < .001 | 2.11 (1.93 to 2.30) | < .001 | 2.31 (2.15 to 2.49) | < .001 | 2.02 (1.87 to 2.18) | < .001 | 2.10 (1.88 to 2.35) | < .001 | 1.86 (1.68 to 2.04) | < .001 |
Waist circumference, per 10 cm | 1.14 (1.10 to 1.18) | < .001 | 1.27 (1.19 to 1.35) | < .001 | 1.07 (1.02 to 1.12) | 0.006 | 1.10 (1.05 to 1.15) | < .001 | ||||
Height, per 10 cm | 1.14 (1.08 to 1.19) | < .001 | 1.17 (1.08 to 1.28) | < .001 | 1.15 (1.08 to 1.23) | < .001 | ||||||
Daily alcohol consumption, high | 1.12 (1.02 to 1.22) | 0.017 | 1.21 (1.07 to 1.37) | 0.002 | 1.27 (1.08 to 1.50) | 0.004 | ||||||
Ever smoker, yes | 1.18 (1.08 to 1.28) | < .001 | 1.18 (1.02 to 1.35) | 0.024 | 1.14 (1.02 to 1.28) | 0.018 | 1.32 (1.17 to 1.49) | < .001 | 1.44 (1.19 to 1.74) | < .001 | ||
Physically active, yes | 0.88 (0.80 to 0.98) | 0.025 | 0.84 (0.72 to 0.99) | 0.035 | ||||||||
Vegetables, per 100 g/day | 0.91 (0.89 to 0.94) | < .001 | 0.90 (0.85 to 0.94) | < .001 | 0.93 (0.89 to 0.97) | 0.001 | 0.92 (0.88 to 0.96) | < .001 | 0.88 (0.82 to 0.93) | < .001 | ||
Fruits, per 100 g/day | ||||||||||||
Dark bread, per 50 g/day | 0.96 (0.93 to 0.99) | 0.017 | 0.94 (0.90 to 0.98) | 0.008 | ||||||||
Dairy products, per 100 g/day | 0.98 (0.96 to 0.99) | 0.007 | 0.96 (0.93 to 0.98) | 0.001 | ||||||||
Red meat, per 50 g/day | ||||||||||||
Poultry per, 50 g/day | ||||||||||||
Processed meat, per 50 g/day | 1.20 (1.10 to 1.31) | < .001 | 1.27 (1.09 to 1.47) | 0.002 | ||||||||
Fish, per 50 g/day | ||||||||||||
Sugar and confectionary, per 50 g/day | ||||||||||||
Soft drinks, per 100 g/day | 1.03 (1.00 to 1.06) | 0.025 | 1.06 (1.02 to 1.10) | 0.006 | ||||||||
Survival functionm (10 years)* | 0.9966 | 0.9953 | 0.9970 | 0.9979 | 0.9968 | 0.9982 | ||||||
Risk Scorem† | 7.156 | 5.802 | 7.137 | 6.8764 | 3.9117 | 3.2985 | ||||||
Absolute Riskm (10 years)‡ | 0.48% | 0.62% | 0.41% | 0.28% | 0.42% | 0.21% |
Model performance: discrimination and calibration
Colorectal cancer | Colon cancer | Rectal cancer | |||||||
---|---|---|---|---|---|---|---|---|---|
Selected predictors | Both sexes | Men | Women | Both sexes | Men | Women | Both sexes | Men | Women |
Age at recruitment, per 10 years | ● | ● | ● | ● | ● | ● | ● | ● | ● |
Waist circumference, per 10 cm | ● | ● | ● | ● | ● | ● | ● | ||
Height, per 10 cm | ● | ● | ● | ● | ● | ||||
Daily alcohol consumption, high | ● | ● | ● | ● | ● | ||||
Ever smoker, yes | ● | ● | ● | ● | ● | ● | ● | ● | |
Physically active, yes | ● | ● | ● | ||||||
Vegetables, per 100 g/day | ● | ● | ● | ● | ● | ● | ● | ● | |
Fruits, per 100 g/day | |||||||||
Dark bread, per 50 g/day | ● | ● | ● | ||||||
Dairy products, per 100 g/day | ● | ● | ● | ● | |||||
Red meat, per 50 g/day | ● | ||||||||
Poultry, per 50 g/day | |||||||||
Processed meat, per 50 g/day | ● | ● | ● | ● | |||||
Fish, per 50 g/day | |||||||||
Sugar and confectionary, per 50 g/day | ● | ||||||||
Soft drinks, per 100 g/day | ● | ● | |||||||
Harrell’s C-index | |||||||||
Full model | |||||||||
Derivation cohort | 0.710 | 0.700 | 0.702 | 0.718 | 0.708 | 0.718 | 0.705 | 0.705 | 0.677 |
Optimism corrected * | 0.708 | 0.697 | 0.700 | 0.716 | 0.707 | 0.715 | 0.704 | 0.703 | 0.668 |
Validation cohort | 0.715 | 0.707 | 0.700 | 0.708 | 0.727 | 0.700 | 0.730 | 0.689 | 0.693 |
Reduced model | |||||||||
Derivation cohort | 0.710 | 0.699 | 0.700 | 0.717 | 0.705 | 0.717 | 0.703 | 0.700 | 0.668 |
Optimism corrected* | 0.709 | 0.698 | 0.699 | 0.716 | 0.704 | 0.715 | 0.701 | 0.698 | 0.667 |
Validation cohort | 0.714 | 0.708 | 0.699 | 0.708 | 0.727 | 0.698 | 0.728 | 0.687 | 0.696 |