Table 2.
Adjusted hazard ratios and 95% confidence intervals for associations of cigarette smoking with biliary tract cancer risk by anatomic site in the Biliary Tract Cancers Pooling Project–summary risk estimates from the random-effects meta-analysis*
| Cigarette smoking | No. of noncases†,‡ | Gallbladder cancer |
Intrahepatic bile duct cancer |
Extrahepatic bile duct cancer |
Ampulla of Vater cancer |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of cases‡ | HR (95% CI) | I2, % | No. of cases‡ | HR (95% CI) | I2, % | No. of cases‡ | HR (95% CI) | I2, % | No. of cases‡ | HR (95% CI) | I2, % | ||
| Ever smoking | |||||||||||||
| No | 1 084 270 | 596 | (Referent) | — | 263 | (Referent) | — | 348 | (Referent) | — | 189 | (Referent) | — |
| Yes | 1 191 039 | 493 | 1.02 (0.89 to 1.17) | 0.0 | 315 | 1.11 (0.93 to 1.33) | 0.0 | 541 | 1.38 (1.17 to 1.62) | 6.1 | 317 | 1.52 (1.24 to 1.86) | 0.0 |
| Smoking status | |||||||||||||
| Never smoker | 1 084 270 | 596 | (Referent) | — | 263 | (Referent) | — | 348 | (Referent) | — | 189 | (Referent) | — |
| Former smoker | 827 061 | 332 | 0.98 (0.84 to 1.14) | 0.0 | 211 | 1.06 (0.87 to 1.30) | 0.0 | 351 | 1.29 (1.09 to 1.53) | 0.0 | 209 | 1.38 (1.11 to 1.72) | 0.0 |
| Current smoker | 362 313 | 161 | 1.18 (0.98 to 1.43) | 0.0 | 104 | 1.30 (1.00 to 1.69) | 0.0 | 190 | 1.69 (1.34 to 2.13) | 15.1 | 108 | 2.22 (1.69 to 2.92) | 0.0 |
| Smoking pack-years | |||||||||||||
| Never smoker | 984 603 | 545 | (Referent) | — | 246 | (Referent) | — | 333 | (Referent) | — | 174 | (Referent) | — |
| >0–20 | 385 482 | 165 | 0.95 (0.79 to 1.14) | 0.0 | 78 | 0.89 (0.67 to 1.19) | 0.0 | 146 | 1.16 (0.93 to 1.45) | 4.0 | 94 | 1.41 (1.07 to 1.85) | 0.0 |
| >20–40 | 223 798 | 112 | 1.19 (0.93 to 1.51) | 10.6 | 76 | 1.35 (0.97 to 1.89) | 16.2 | 126 | 1.53 (1.12 to 2.10) | 38.4 | 72 | 1.84 (1.27 to 2.66) | 22.0 |
| >40 | 148 402 | 68 | 1.16 (0.88 to 1.52) | 0.0 | 48 | 1.29 (0.92 to 1.81) | 0.0 | 93 | 1.76 (1.24 to 2.51) | 37.7 | 46 | 1.79 (1.11 to 2.90) | 30.8 |
| P trend § | .39 | .08 | <.001 | .005 | |||||||||
| Continuous per 10 pack-years | — | — | 1.03 (0.99 to 1.07) | 0.0 | — | 1.06 (1.02 to 1.11) | 3.1 | — | 1.10 (1.05 to 1.16) | 39.5 | — | 1.09 (1.02 to 1.16) | 36.6 |
| Smoking duration (years) | |||||||||||||
| Never smoker | 1 070 496 | 594 | (Referent) | — | 258 | (Referent) | — | 345 | (Referent) | — | 187 | (Referent) | — |
| >0–10 | 164 873 | 56 | 1.07 (0.80 to 1.43) | 0.0 | 41 | 1.46 (1.02 to 2.09) | 0.0 | 51 | 1.46 (1.07 to 1.99) | 0.0 | 30 | 1.53 (1.01 to 2.31) | 0.0 |
| >10–20 | 194 455 | 57 | 0.93 (0.67 to 1.30) | 15.2 | 39 | 1.23 (0.85 to 1.79) | 0.0 | 56 | 1.20 (0.88 to 1.64) | 0.0 | 37 | 1.81 (1.18 to 2.76) | 6.5 |
| >20–40 | 501 925 | 227 | 1.11 (0.94 to 1.32) | 0.0 | 128 | 1.06 (0.82 to 1.36) | 5.9 | 225 | 1.29 (1.03 to 1.62) | 20.5 | 126 | 1.57 (1.15 to 2.14) | 20.3 |
| >40 | 127 3389 | 64 | 1.06 (0.72 to 1.55) | 44.1 | 41 | 1.29 (0.89 to 1.87) | 3.2 | 93 | 1.96 (1.47 to 2.63) | 13.5 | 55 | 2.18 (1.56 to 3.06) | 0.0 |
| P trend § | .86 | .57 | .008 | <.001 | |||||||||
| Continuous per 10 years | — | — | 1.00 (0.96 to 1.05) | 7.1 | — | 1.02 (0.94 to 1.10) | 25.9 | — | 1.10 (1.02 to 1.19) | 47.8 | — | 1.14 (1.07 to 1.21) | 0.0 |
| Smoking intensity (cigarettes/day) | |||||||||||||
| Never smoker | 984 603 | 545 | (Referent) | — | 246 | (Referent) | — | 333 | (Referent) | — | 174 | (Referent) | — |
| >0–10 | 316 037 | 166 | 1.06 (0.88 to 1.28) | 0.0 | 60 | 0.86 (0.61 to 1.22) | 13.1 | 128 | 1.20 (0.97 to 1.49) | 0.0 | 87 | 1.49 (1.14 to 1.96) | 0.0 |
| >10–20 | 336 669 | 151 | 1.13 (0.93 to 1.37) | 0.0 | 108 | 1.33 (1.03 to 1.72) | 0.0 | 185 | 1.62 (1.21 to 2.17) | 41.6 | 97 | 1.87 (1.20 to 2.91) | 50.8 |
| >20–40 | 230 576 | 91 | 1.13 (0.88 to 1.45) | 0.0 | 77 | 1.46 (1.09 to 1.95) | 0.0 | 135 | 1.74 (1.39 to 2.19) | 0.0 | 78 | 1.76 (1.29 to 2.40) | 0.0 |
| >40 | 46 656 | 17 | 1.75 (1.00 to 3.06) | 8.0 | 19 | 2.15 (1.15 to 4.00) | 17.7 | 24 | 3.00 (1.17 to 7.73) | 60.4 | 13 | 2.02 (0.92 to 4.43) | 17.9 |
| P trend § | .34 | .001 | <.001 | .001 | |||||||||
| Continuous per 10 cigarettes | — | — | 1.04 (0.98 to 1.10) | 0.0 | — | 1.12 (1.05 to 1.20) | 0.0 | — | 1.17 (1.10 to 1.24) | 11.1 | — | 1.13 (1.05 to 1.21) | 0.0 |
Adjusted for sex (male, female), race (white, black, Asian and Pacific Islander, other), education (less than high school graduate, high school graduate, some college or post-high school training), body mass index in kg/m2 (<18.5, 18.5–<25, 25–<30, ≥30), history of diabetes (ever vs never diagnosed), birth cohort (1870–1899, 1900–1909, 1910–1919, 1920–1929, 1930–1939, 1940–1949, 1950–1959, 1960–1982), and alcoholic drinks per day (0, >0–0.5, >0.5–1, 1–<3, ≥3). CI = confidence interval; HR= hazard ratio.
No. of noncases: The same noncase group was used for all analyses, except for analyses of intrahepatic bile duct cancer. The Radiation Effects Research Foundation Life Span Study (RERF) did not provide information on intrahepatic bile duct cancer diagnoses, so this study was excluded from these analyses and the maximum noncase group was thus n = 2 267 501.
No. of noncases and No. of cases: Some counts do not add to totals because of missing data. Numbers represent the maximum possible number of participants included in each analysis.
P trend: Two-sided P value for the ordinal variable, calculated using the Wald test.