Article Figures & Data
Figures
- Figure 1.
Predicted probabilities of 1 year lung cancer incidence, for a variety of smoking profiles, assuming an average smoking intensity of 20 cpd. A, probability of lung cancer in current smokers by age, for different ages of commencement of smoking. B, probability of lung cancer in current smokers by smoking duration, for different ages of commencement of smoking. C, probability of lung cancer in former smokers by age, for different ages of commencement of smoking assuming a smoking duration of 20 to 30 years. D, probability of lung cancer in former smokers by age, for different durations of smoking assuming commencement of smoking between 22 and 26 years old.
- Figure 2.
Calibration of risk models for (A) current smokers, (B) former smokers, and (C) the combined group of ever smokers. Plots show predicted and observed estimates of 1-year lung cancer incidence in the test set by deciles of predicted risk. Probabilities were calculated for each year each individual was followed. Bars at each decile show the 95% confidence interval for the predicted probability. The observed number of cases and person-years of exposure in the top 3 deciles are shown at the bottom of the figure.
Tables
- Table 1.
Distribution of population variables in the training and test sets by smoking and disease status
Training set Test set Current smokers Former smokers Current smokers Former smokers No lung cancer Lung cancer No lung cancer Lung cancer No lung cancer Lung cancer No lung cancer Lung cancer Missing (%) Total 73,677 (98.9) 820 (1.1) 77,328 (99.61) 304 (0.39) 8,187 (98.89) 92 (1.11) 8,593 (99.61) 34 (0.39) Number of genotyped individuals, n (%) 508 (44.8) 626 (55.2) 678 (74.34) 234 (25.66) 57 (47.9) 62 (52.1) 72 (72.73) 27 (27.27) 98.83 Sociodemographic Sex, n (%) Male 45,647 (99.23) 354 (0.77) 43,178 (99.76) 104 (0.24) 5,073 (99.24) 39 (0.76) 4,870 (99.75) 12 (0.25) 0 Female 70,169 (98.84) 820 (1.16) 74,009 (99.59) 304 (0.41) 7,774 (98.83) 92 (1.17) 8,225 (99.59) 34 (0.41) Dead at censoring, n (%)a 3,508 (100) 0 (0) 3,319 (100) 0 (0) 413 (100) 0 (0) 368 (100) 0 (0) 0 Age, mean (SD), y 57.5 (8.8) 62 (7.3) 60.5 (9.5) 65.6 (8.8) 57.4 (8.8) 60.6 (8.2) 60.5 (9.6) 65.8 (8.5) 0 Age at recruitment, mean (SD), y 49.5 (8.7) 57.2 (7.2) 52.5 (9.4) 60.8 (8.4) 49.5 (8.8) 56.1 (8.1) 52.5 (9.5) 60.8 (8.3) 0 Follow-up, mean (SD), y 7.9 (2) 4.8 (2.6) 8 (2) 4.8 (2.6) 7.9 (2) 4.5 (2.9) 8 (2) 4.9 (2.3) 0 BMI, mean (SD), kg/m2 25.7 (4.1) 25.7 (4.5) 26.4 (4.1) 26.7 (3.6) 25.7 (4.2) 26 (4.3) 26.3 (4.1) 27 (2.5) 12.56 Education, n (%) High school and below 60,415 (98.84) 710 (1.16) 56,190 (99.54) 259 (0.46) 6,642 (98.74) 85 (1.26) 6,201 (99.57) 27 (0.43) 4.68 Greater than high school 11,817 (99.32) 81 (0.68) 17,532 (99.89) 20 (0.11) 1,390 (99.57) 6 (0.43) 1,984 (99.7) 6 (0.3) Medical history Hay fever, n (%) No 15,925 (99.1) 145 (0.9) 16,526 (99.73) 45 (0.27) 1,784 (98.84) 21 (1.16) 1,815 (99.78) 4 (0.22) 73.53 Yes 2,664 (99.48) 14 (0.52) 3,963 (99.67) 13 (0.33) 301 (99.34) 2 (0.66) 467 (99.57) 2 (0.43) Asthma, n (%) No 30,788 (99.16) 260 (0.84) 27,690 (99.73) 76 (0.27) 3,393 (99.09) 31 (0.91) 3,071 (99.71) 9 (0.29) 61.46 Yes 1,521 (98.51) 23 (1.49) 2,103 (98.92) 23 (1.08) 161 (98.17) 3 (1.83) 269 (99.26) 2 (0.74) Family history of cancer, n (%) No 9,730 (98.81) 117 (1.19) 10,880 (99.32) 74 (0.68) 1,098 (99.01) 11 (0.99) 1,235 (99.2) 10 (0.8) 84.02 Yes 1,051 (98.32) 18 (1.68) 1,409 (99.09) 13 (0.91) 121 (99.18) 1 (0.82) 157 (98.74) 2 (1.26) Smoking exposures Smoking intensity, mean (SD), cpd 13.5 (7.5) 17.6 (7.4) 13.1 (9.2) 17.8 (10.9) 13.5 (7.4) 17.2 (7.9) 13 (9.2) 17.1 (11.6) 0 Smoking duration, mean (SD), y 30.3 (9.7) 39.5 (8.2) 19 (10.7) 31.4 (12.1) 30.2 (9.8) 38.8 (8.4) 18.9 (10.7) 31.7 (11) 0 Quit time, mean (SD), y 0 (0.1) 0 (0.1) 15 (9.9) 11.9 (9.3) 0 (0.1) 0 (0.1) 15 (9.9) 10.8 (7.4) 0 Age start smoking, mean (SD), y 27.2 (6.1) 22.5 (5.1) 26.5 (4.8) 22.3 (5.2) 27.2 (6.2) 21.8 (4.2) 26.5 (4.9) 23.2 (5.9) 0 Cigarettes per day ≤15 28,222 (98.21) 515 (1.79) 29,174 (99.37) 186 (0.63) 3,203 (98.31) 55 (1.69) 3,242 (99.42) 19 (0.58) 0 >15 45,455 (99.33) 305 (0.67) 48,154 (99.76) 118 (0.24) 4,984 (99.26) 37 (0.74) 5,351 (99.72) 15 (0.28) Occupational exposures Silica, n (%) Not exposed 44,057 (98.64) 609 (1.36) 43,604 (99.51) 216 (0.49) 4,944 (98.58) 71 (1.42) 4,870 (99.47) 26 (0.53) 42.06 Exposed 1,125 (97.74) 26 (2.26) 1,153 (99.31) 8 (0.69) 118 (98.33) 2 (1.67) 104 (99.05) 1 (0.95) PAH, n (%) Not exposed 39,750 (98.72) 514 (1.28) 39,620 (99.51) 194 (0.49) 4,419 (98.55) 65 (1.45) 4,412 (99.53) 21 (0.47) 42.06 Exposed 5,432 (97.82) 121 (2.18) 5,137 (99.42) 30 (0.58) 643 (98.77) 8 (1.23) 562 (98.94) 6 (1.06) Metal, n (%) Not exposed 32,596 (98.65) 447 (1.35) 34,035 (99.56) 150 (0.44) 3,661 (98.79) 45 (1.21) 3,831 (99.56) 17 (0.44) 46.19 Exposed 6,827 (98) 139 (2) 7,521 (99.31) 52 (0.69) 760 (97.31) 21 (2.69) 806 (99.02) 8 (0.98) Asbestos, n (%) Not exposed 39,734 (98.73) 513 (1.27) 38,974 (99.54) 182 (0.46) 4,425 (98.75) 56 (1.25) 4,334 (99.54) 20 (0.46) 42.06 Exposed 5,448 (97.81) 122 (2.19) 5,783 (99.28) 42 (0.72) 637 (97.4) 17 (2.6) 640 (98.92) 7 (1.08) -
↵aNumbers are taken at time of censoring, cases were censored at diagnosis, before death.
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- Table 2.
Weibull parameters and HRs of smoking intensity used in Equation (A) for the lung cancer incidence and death models for current and former smokers
Current smokers Lung cancer incidence Death HR (95% CI) β1 P HR (95% CI) β2 P Smoking intensity ≤ 15 1.111 (1.084–1.139) <10−16 1.051 (1.041–1.062) <10−16 Weibull hazard parameters Weibull hazard parameters Strata Shape (95% CI) λ1 Scale (95% CI) γ1 Shape (95% CI) λ2 Scale (95% CI) γ2 t ≤ 18 3.819 (3.750–3.869) 0.999 (0.772–1.162) 3.690 (3.659–3.713) 1.220 (1.105–1.302) 18 < t ≤ 20 4.056 (3.966–4.121) 1.071 (0.870–1.215) 3.774 (3.748–3.793) 1.312 (1.210–1.384) 20 < t ≤ 22 4.230 (4.134–4.299) 1.298 (1.144–1.408) 3.859 (3.839–3.873) 1.560 (1.489–1.611) 22 < t ≤ 24 4.339 (4.234–4.414) 1.518 (1.374–1.621) 3.944 (3.924–3.958) 1.775 (1.715–1.818) 24 < t ≤ 26 4.380 (4.258–4.468) 1.679 (1.519–1.794) 3.979 (3.958–3.995) 1.925 (1.865–1.969) 26 < t ≤ 28 4.567 (4.361–4.714) 1.517 (1.294–1.677) 4.049 (4.017–4.071) 1.854 (1.773–1.911) 28 < t ≤ 30 4.506 (4.278–4.670) 1.615 (1.344–1.809) 4.096 (4.049–4.130) 1.838 (1.727–1.917) 30 < t 4.504 (4.317–4.637) 1.684 (1.454–1.848) 4.069 (4.040–4.090) 1.912 (1.835–1.966) Former smokers Lung cancer incidence Death HR (95% CI) β1 P HR (95% CI) β2 P Smoking intensity ≤ 15 1.043 (1.012–1.076) 0.007 1.015 (1.006–1.023) <10−16 Weibull hazard parameters Weibull hazard parameters Strata Shape (95% CI) λ1 Scale (95% CI) γ1 Shape (95% CI) λ2 Scale (95% CI) γ2 t ≤ 22; s ≤ 20 4.987 (4.372–5.427) 0.750 (0.359–1.029) 3.754 (3.722–3.776) 1.210 (1.128–1.269) 20 < s ≤ 30 4.723 (4.242–5.066) 0.819 (0.409–1.112) 3.750 (3.726–3.767) 1.511 (1.428–1.570) 30 < s 4.321 (4.140–4.450) 1.032 (0.733–1.246) 3.800 (3.785–3.810) 1.669 (1.603–1.716) 22 < t ≤ 26; s ≤ 20 5.179 (4.537–5.638) 1.165 (0.795–1.430) 4.008 (3.975–4.032) 1.621 (1.555–1.668) 20 < s ≤ 30 4.786 (4.335–5.108) 1.353 (0.989–1.612) 3.975 (3.942–3.998) 1.742 (1.663–1.799) 30 < s ≤ 36 4.651 (4.132–5.022) 1.460 (0.945–1.829) 3.954 (3.921–3.977) 1.835 (1.734–1.907) 36 < s ≤ 42 4.654 (4.034–5.097) 1.318 (0.639–1.804) 3.928 (3.903–3.945) 2.129 (2.018–2.208) 42 < s 4.366 (4.090–4.563) 1.662 (1.136–2.038) 3.982 (3.961–3.998) 2.150 (2.040–2.229) t > 26; s ≤ 20 5.563 (4.668–6.202) 1.088 (0.640–1.409) 4.123 (4.087–4.148) 1.769 (1.698–1.820) 20 < s ≤ 30 4.680 (4.223–5.007) 1.705 (1.249–2.032) 4.058 (4.026–4.082) 1.865 (1.781–1.926) 30 < s ≤ 36 4.491 (4.062–4.797) 1.879 (1.312–2.283) 4.020 (3.986–4.044) 2.148 (2.027–2.234) 36 < s ≤ 42 4.241 (3.990–4.420) 2.336 (1.754–2.751) 3.999 (3.968–4.021) 2.360 (2.213–2.465) 42 < s 4.177 (4.052–4.266) 2.574 (2.123–2.896) 4.041 (4.007–4.066) 2.490 (2.295–2.629) NOTE: Parameter estimates are based on maximum likelihood estimates, 95% CIs are in parentheses. Time zero set to 35 years old.
Abbreviations: s, smoking duration; t, age start smoke.
- Table 3.
HRs for effect of exposures in current and former smokers estimated in the training set and their predictive value in the test set
HR (95% CI) P P for improvement in AUC tdNRI Change P Covariate Current Former Current Former Current Former Current Former Current Former Sex: female 1, male 0. 1.35 (1.16–1.57) 1.2 (0.91–1.59) 0.000126 0.194 − 0.885 −0.346 −0.321 0.99 0.937 BMI 0.963 (0.946–0.98) 0.96 (0.929–0.992) 3.7 × 10−5 0.0148 − − −0.0709 −0.206 0.687 0.82 Education level (greater than high school) 0.944 (0.751–1.19) 0.436 (0.275–0.691) 0.62 0.000418 0.243 − 0.235 −0.0763 0.01 0.637 Hay fever 0.593 (0.335–1.05) 0.901 (0.494–1.64) 0.0728 0.734 + + 0.233 0.12 0.139 0.366 Asthma 0.85 (0.546–1.32) 1.58 (0.961–2.6) 0.474 0.071 + + 0.0437 −0.0127 0.346 0.504 Family history of cancer 1.27 (0.758–2.11) 1.23 (0.694–2.16) 0.368 0.484 + + −0.217 −0.235 0.9 0.845 Chr15q25 1.13 (1.01–1.27) 1.14 (0.933–1.38) 0.0336 0.202 − 0.726 0.309 0.406 0.381 0.23 Chr5p15 0.954 (0.845–1.08) 1.06 (0.865–1.3) 0.442 0.572 0.765 0.885 1.3 −0.495 0.067 0.808 Occupational exposures Silica 0.893 (0.602–1.33) 0.851 (0.349–2.07) 0.574 0.722 + + −0.0252 −0.0907 0.684 0.945 PAH 0.988 (0.808–1.21) 0.869 (0.586–1.29) 0.906 0.485 0.671 − 0.0177 −0.194 0.428 0.871 Metal 0.961 (0.794–1.16) 1.23 (0.866–1.74) 0.68 0.249 − 0.308 −0.385 0.281 0.996 0.06 Asbestos 0.943 (0.775–1.15) 1.05 (0.738–1.49) 0.558 0.784 − 0.603 −0.24 0.296 0.986 0.029 NOTE: Exposure effects are conditional on lifetime exposure to cigarette smoke. P value for improvement in AUC and tdNRI compares predictive performance of model with and without covariate (tdNRI P values were calculated by permutation). AUC P values are not shown for covariates whose inclusion decreased the AUC (denoted by −) and there were fewer than 5 exposed cases (denoted by +).
- Table 4.
Predictive performance, measured by the AUC, of our model and the Bach model for predicting 1- and 5-year cancer risk in the EPIC test set
Current smokers Former smokers Ever smokers Bach high-risk group One year Controls 8,187 8,593 16,780 4,934 Cases 92 34 126 82 New 0.824 (0.783–0.865) 0.830 (0.762–0.899) 0.843 (0.810–0.875) 0.753 (0.700–0.806) Bach 0.732 (0.683–0.780) 0.787 (0.710–0.864) 0.775 (0.737–0.813) 0.656 (0.595–0.717) P 1.25 × 10−5 0.0957 3.91 × 10−6 1.61 × 10−4 Five years Controls 7,444 6,535 13,979 4,049 Cases 43 10 53 37 New 0.767 (0.701–0.832) 0.715 (0.532–0.898) 0.787 (0.728–0.847) 0.681 (0.597–0.765) Bach 0.749 (0.686–0.813) 0.753 (0.583–0.922) 0.743 (0.685–0.802) 0.589 (0.510–0.669) P 0.362 0.118a 0.024 0.0035 NOTE: Bach high-risk group are individuals between 50 and 75 years old who have smoked 10 to 60 cpd for 25 to 55 years. Also shown is the P value for improvement in AUC of our model compared with the Bach model.
aAUC for 5-year prediction of former smokers is higher using Bach model, therefore P value refers to superiority of Bach model relative to the new model.
Volume 5, Issue 6
