Background
Methods
Study population
Definition and covariates
Main outcome measures
Statistical analyses
Ethics statement
Results
Baseline characteristics of this cohort
Never smoker | Former smoker | Smoker | |||||
---|---|---|---|---|---|---|---|
No COPD | COPD | No COPD | COPD | No COPD | COPD | P | |
Number | 313,553 (65.45) | 7789 (1.63) | 41,359 (8.63) | 1085 (0.23) | 112,627 (23.51) | 2677 (0.56) | |
Age (years) | 53.64 ± 9.62 | 62.23 ± 9.87 | 51.65 ± 9.12 | 62.43 ± 10.16 | 50.92 ± 8.74 | 61.29 ± 9.83 | < 0.001 |
Gender (male), N (%) | 107,393 (34.25) | 2799 (35.94) | 39,292 (95.00) | 1005 (92.63) | 106,695 (94.73) | 2368 (88.46) | < 0.001 |
BMI (kg/m2) | 24.08 ± 3.01 | 24.02 ± 3.39 | 24.31 ± 2.73 | 23.18 ± 3.05 | 23.73 ± 2.94 | 22.97 ± 3.28 | < 0.001 |
< 20 | 23,181 (7.39) | 847 (10.87) | 2205 (5.33) | 157 (14.47) | 11,102 (9.86) | 514 (19.20) | < 0.001 |
20 ≤ < 25 | 178,681 (56.99) | 4071 (52.27) | 22,958 (55.51) | 642 (59.17) | 65,174 (57.87) | 1466 (54.76) | < 0.001 |
25 ≤ < 30 | 101,536 (32.38) | 2556 (32.82) | 15,247 (36.87) | 265 (24.42) | 34,045 (30.23) | 633 (23.65) | < 0.001 |
30 ≤ | 10,155 (3.24) | 315 (4.04) | 949 (2.29) | 21 (1.94) | 2306 (2.05) | 64 (2.39) | < 0.001 |
Systolic blood pressure (mmHg) | 126.71 ± 18.55 | 130.61 ± 19.21 | 128.56 ± 17.16 | 130.07 ± 18.70 | 127.71 ± 17.55 | 128.88 ± 18.59 | < 0.001 |
Diastolic blood pressure (mmHg) | 97.28 ± 33.29 | 100.50 ± 38.18 | 99.56 ± 32.21 | 101.26 ± 44.08 | 100.40 ± 37.72 | 101.86 ± 34.78 | < 0.001 |
Fasting serum glucose (mg/dL) | 200.88 ± 38.50 | 201.56 ± 39.47 | 201.17 ± 37.52 | 196.79 ± 42.59 | 199.10 ± 38.39 | 195.80 ± 42.63 | < 0.001 |
Total cholesterol (mg/dL) | 313,553 (65.45) | 7789 (1.63) | 41,359 (8.63) | 1085 (0.23) | 112,627 (23.51) | 2677 (0.56) | < 0.001 |
Exercise level | |||||||
Non exercise | 187,422(60.81) | 5387 (70.08) | 16,159 (39.74) | 619 (58.18) | 59,485 (52.97) | 1848 (69.42) | < 0.001 |
Once or twice a week | 63,023 (20.45) | 1078 (14.02) | 13,986 (34.40) | 239 (22.46) | 33,756 (30.06) | 450 (16.90) | |
At least three times a week | 57,778 (18.75) | 1225 (15.90) | 10,517 (25.86) | 206 (19.36) | 19,063 (16.97) | 364 (13.67) | |
Incident rate of lung cancer per 100,000 person year: average of six arms = 278 | 216 | 757 | 271 | 1266 | 394 | 1560 | < 0.001 |
Prevalence of cancer for 12 years, N (%) | |||||||
Lung cancer (C33-C34) | 7669 (2.44) | 609 (7.82) | 1263 (3.05) | 129 (11.89) | 4899 (4.35) | 398 (14.87) | < 0.001 |
Stomach cancer (C16) | 7979 (2.54) | 310 (3.98) | 1464 (3.54) | 64 (5.90) | 4170 (3.70) | 143 (5.34) | < 0.001 |
Colorectal cancer (C18-C20) | 12,126 (3.87) | 505 (6.48) | 1847 (4.47) | 65 (5.99) | 4783 (4.25) | 203 (7.58) | < 0.001 |
Liver cancer (C22) | 12,681 (4.04) | 446 (5.73) | 2091 (5.06) | 81 (7.47) | 6131 (5.44) | 188 (7.02) | < 0.001 |
AML (C92.0) | 181 (0.06) | 5 (0.06) | 19 (0.05) | 1 (0.09) | 74 (0.07) | 3 (0.11) | 0.600 |
Esophageal cancer (C15) | 463 (0.15) | 29 (0.37) | 124 (0.30) | 3 (0.28) | 474 (0.42) | 15 (0.56) | < 0.001 |
Bladder cancer (C67) | 2367 (0.75) | 100 (1.28) | 426 (1.03) | 18 (1.66) | 1083 (0.96) | 39 (1.46) | < 0.001 |
Kidney cancer (C64-C66) | 1740 (0.55) | 58 (0.74) | 276 (0.67) | 12 (1.11) | 729 (0.65) | 24 (0.90) | < 0.001 |
Past medical history, N (%) | |||||||
Hypertension | 29,436 (9.39) | 1257 (16.14) | 3334 (8.06) | 143 (13.18) | 5974 (5.30) | 282 (10.53) | < 0.001 |
Diabetes mellitus | 12,904 (4.12) | 539 (6.92) | 1949 (4.71) | 65 (5.99) | 4559 (4.05) | 173 (6.46) | < 0.001 |
Risk factors for the development of lung cancer
Cox regression analysis | ||||
---|---|---|---|---|
Univariate Hazard ratio (95% CI) | p-value | Multivariate Hazard ratio (95% CI) | p-value | |
Age (years) | 1.072 (1.070–1.074) | < 0.001 | 1.074 (1.072–1.076) | < 0.001 |
Male (vs female) | 1.866 (1.803–1.931) | < 0.001 | 1.789 (1.717–1.864) | < 0.001 |
BMI (kg/m2) | < 0.001 | < 0.001 | ||
< 20 | 1.661(1.582–1.744) | 1.323 (1.256–1.393) | ||
20 ≤ < 25 | Reference | Reference | ||
25 ≤ < 30 | 0.852 (0.769–0.945) | 0.885 (0.795–0.985) | ||
30 ≤ | 0.446 (0.396–0.501) | 0.837 (0.705–0.994) | ||
History of hypertension | 1.414(1.344–1.488) | < 0.001 | 0.990(0.939–1.044) | 0.718 |
History of diabetes mellitus | 1.579(1.477–1.688) | < 0.001 | 1.186(1.108–1.269) | < 0.001 |
COPD diagnosis | 3.752(3.530–3.988) | < 0.001 | 2.046(1.922–2.177) | < 0.001 |
Exercise level | < 0.001 | < 0.001 | ||
Never Exercise | 1.178 (1.129–1.229) | 1.145 (1.095–1.198) | ||
1–2 times a week | 0.888 (0.816–0.966) | 1.010 (0.925–1.103) | ||
≥ 3 times a week | Reference | Reference | ||
Smoking status | < 0.001 | < 0.001 | ||
Never smoker | Reference | Reference | ||
Former smoker | 1.277(1.205–1.352) | 1.108(1.042–1.178) | ||
Current smoker | 1.860(1.797–1.926) | 1.689(1.622–1.759) |
Risk factors for the development of other major cancers including stomach cancer, colorectal cancer, liver cancer, esophageal cancer, and bladder cancer
COPD as a risk factor for the development of major cancers
Hazard Ratio (95% CI) | ||||||
---|---|---|---|---|---|---|
Model 1 Hazard ratio (95% CI) | p-value | Model 2 Hazard ratio (95% CI) | p-value | Model 3 Hazard ratio (95% CI) | p-value | |
Lung cancer | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 1.100 (1.035–1.170) | 0.002 | 1.100 (1.035–1.169) | 0.002 | 1.108 (1.043–1.178) | < 0.001 |
Smoker without COPD | 1.752 (1.683–1.823) | < 0.001 | 1.749 (1.681–1.821) | < 0.001 | 1.689 (1.622–1.759) | < 0.001 |
Never smoker with COPD | 2.086 (1.960–2.220) | < 0.001 | 2.086 (1.960–2.220) | < 0.001 | 2.046 (1.922–2.177) | < 0.001 |
Former smoker with COPD | 2.295 (2.105–2.503) | < 0.001 | 2.294 (2.104–2.502) | < 0.001 | 2.267 (2.079–2.472) | 0.001 |
Current smoker with COPD | 3.654 (3.396–3.932) | < 0.001 | 3.650 (3.392–3.927) | < 0.001 | 3.456 (3.211–3.720) | < 0.001 |
Stomach cancer | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 1.105 (1.042–1.172) | 0.001 | 1.104 (1.041–1.171) | 0.001 | 1.111 (1.048–1.178) | < 0.001 |
Smoker without COPD | 1.249 (1.198–1.302) | < 0.001 | 1.249 (1.197–1.302) | < 0.001 | 1.289 (1.184–1.289) | < 0.001 |
Never smoker with COPD | 1.067 (0.976–1.167) | 0.154 | 1.067 (0.976–1.167) | 0.155 | 1.056 (0.966–1.155) | 0.231 |
Former smoker with COPD | 1.179 (1.060–1.312) | 0.002 | 1.178 (1.060–1.311) | 0.003 | 1.174 (1.055–1.306) | 0.003 |
Current smoker with COPD | 1.333 (1.208–1.470) | < 0.001 | 1.332 (1.208–1.470) | < 0.001 | 1.305 (1.183–1.440) | < 0.001 |
Colorectal cancer | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 1.045 (0.992–1.102) | 0.096 | 1.043 (0.990–1.099) | 0.113 | 1.046 (0.992–1.102) | 0.095 |
Smoker without COPD | 1.086 (1.046–1.128) | < 0.001 | 1.089 (1.048–1.131) | < 0.001 | 1.088 (1.047–1.130) | < 0.001 |
Never smoker with COPD | 1.277 (1.197–1.374) | < 0.001 | 1.277 (1.186–1.374) | < 0.001 | 1.273 (1.183–1.370) | < 0.001 |
Former smoker with COPD | 1.335 (1.221–1.460) | < 0.001 | 1.332 (1.218–1.456) | < 0.001 | 1.331 (1.217–1.455) | < 0.001 |
Current smoker with COPD | 1.387 (1.278–1.505) | < 0.001 | 1.390 (1.281–1.509) | < 0.001 | 1.385 (1.276–1.503) | < 0.001 |
Liver cancer | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 1.034 (0.985–1.086) | 0.181 | 1.031 (0.982–1.083) | 0.219 | 1.040 (0.990–1.093) | 0.116 |
Smoker without COPD | 1.168 (1.128–1.209) | < 0.001 | 1.168 (1.128–1.210) | < 0.001 | 1.162 (1.122–1.204) | < 0.001 |
Never smoker with COPD | 1.229 (1.139–1.322) | < 0.001 | 1.228 (1.138–1.325) | < 0.001 | 1.217 (1.128–1.313) | < 0.001 |
Former smoker with COPD | 1.271 (1.162–1.391) | < 0.001 | 1.266 (1.157–1.386) | < 0.001 | 1.266 (1.157–1.386) | < 0.001 |
Current smoker with COPD | 1.435 (1.321–1.560) | < 0.001 | 1.434 (1.320–1.559) | < 0.001 | 1.415 (1.302–1.537) | < 0.001 |
Hazard Ratio (95% CI) | ||||||
---|---|---|---|---|---|---|
Model 1 Hazard ratio (95% CI) | p-value | Model 2 Hazard ratio (95% CI) | p-value | Model 3 Hazard ratio (95% CI) | p-value | |
AML | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 0.617 (0.382–0.998) | 0.049 | 0.616 (0.381–0.996) | 0.048 | 0.632 (0.391–1.022) | 0.061 |
Smoker without COPD | 0.922 (0.684–1.242) | 0.593 | 0.925 (0.686–1.246) | 0.608 | 0.914 (0.678–1.233) | 0.556 |
Never smoker with COPD | 1.064 (0.544–2.083) | 0.856 | 1.064 (0.544–2.082) | 0.857 | 1.047 (0.535–2.049) | 0.895 |
Former smoker with COPD | 0.657 (0.289–1.494) | 0.316 | 0.655 (0.288–1.491) | 0.314 | 0.661 (0.291–1.505) | 0.324 |
Current smoker with COPD | 0.981 (0.473–2.037) | 0.959 | 0.984 (0.474–2.043) | 0.965 | 0.957 (0.460–1.989) | 0.905 |
Esphageal cancer | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 1.303 (1.061–1.600) | 0.012 | 1.303 (1.061–1.599) | 0.012 | 1.304 (1.062–1.601) | 0.011 |
Smoker without COPD | 2.082(1.810–2.395) | < 0.001 | 2.080 (1.808–2.394) | < 0.001 | 1.968 (1.709–2.267) | < 0.001 |
Never smoker with COPD | 0.973 (0.722–1.312) | 0.858 | 0.973 (0.722–1.312) | 0.858 | 0.945 (0.700–1.274) | 0.708 |
Former smoker with COPD | 1.268 (0.885–1.817) | 0.197 | 1.268 (0.884–1.817) | 0.197 | 1.231 (0.859–1.765) | 0.257 |
Current smoker with COPD | 2.026 (1.460–2.810) | < 0.001 | 2.024 (1.459–2.808) | < 0.001 | 1.859 (1.338–2.583) | < 0.001 |
Bladder cancer | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 1.090 (0.977–1.216) | 0.121 | 1.088 (0.975–1.214) | 0.129 | 1.089 (0.976–1.215) | 0.127 |
Smoker without COPD | 1.131 (1.044–1.225) | 0.003 | 1.136 (1.049–1.231) | 0.002 | 1.142 (1.053–1.237) | 0.001 |
Never smoker with COPD | 1.145 (0.973–1.347) | 0.104 | 1.145 (0.973–1.347) | 0.103 | 1.146 (0.974–1.348) | 0.101 |
Former smoker with COPD | 1.248 (1.027–1.516) | 0.026 | 1.246 (1.026–1.514) | 0.027 | 1.247 (1.027–1.516) | 0.026 |
Current smoker with COPD | 1.295 (1.081–1.550) | 0.005 | 1.301(1.087–1.558) | 0.004 | 1.308 (1.092–1.566) | 0.004 |
Kidney cancer | ||||||
Never smoker without COPD | Reference | Reference | Reference | |||
Former smoker without COPD | 1.002 (0.875–1.148) | 0.975 | 0.998 (0.871–1.143) | 0.974 | 0.999 (0.873–1.144) | 0.992 |
Smoker without COPD | 1.054 (0.956–1.163) | 0.288 | 1.066 (0.967–1.176) | 0.198 | 1.075 (0.974–1.185) | 0.152 |
Never smoker with COPD | 1.076 (0.870–1.331) | 0.499 | 1.076 (0.870–1.330) | 0.501 | 1.077 (0.871–1.332) | 0.493 |
Former smoker with COPD | 1.079 (0.839–1.386) | 0.555 | 1.073 (0.835–1.379) | 0.581 | 1.076 (0.838–1.383) | 0.565 |
Current smoker with COPD | 1.135 (0.899–1.432) | 0.287 | 1.147 (0.909–1.447) | 0.247 | 1.157 (0.917–1.461) | 0.219 |