Table 2.
Association between 11 circulating markers of inflammation and lung cancer risk in the replication study, in the discovery study, and in pooled data from the two studies combined
| Replication study | Discovery study | Pooled estimate | ||||
|---|---|---|---|---|---|---|
| Marker | Category | Lung cancer case patients | Control subjects | ORs (95% CIs)* | ORs (95% CIs)* | ORs (95% CIs)* |
| CRP | 1 | 112 | 156 | 1.0 | 1.0 | 1.0 |
| 2 | 99 | 156 | 0.94 (0.63 to 1.38) | 1.58 (1.06 to 2.35) | 1.21 (0.92 to 1.59) | |
| 3 | 121 | 156 | 1.09 (0.75 to 1.59) | 1.69 (1.14 to 2.51) | 1.34 (1.03 to 1.75) | |
| 4 | 192 | 156 | 1.77 (1.23 to 2.54) | 2.27 (1.51 to 3.41) | 1.99 (1.52 to 2.61) | |
| Ptrend† | <.001 | <.001 | <.001 | |||
| SAA | 1 | 95 | 156 | 1.0 | 1.0 | 1.0 |
| 2 | 138 | 156 | 1.84 (1.27 to 2.66) | 1.21 (0.83 to 1.77) | 1.51 (1.16 to 1.96) | |
| 3 | 147 | 156 | 1.90 (1.31 to 2.75) | 1.59 (1.08 to 2.33) | 1.72 (1.32 to 2.25) | |
| 4 | 144 | 156 | 1.88 (1.28 to 2.76) | 2.18 (1.48 to 3.22) | 2.03 (1.55 to 2.66) | |
| Ptrend† | .003 | <.001 | <.001 | |||
| sTNFRII | 1 | 102 | 156 | 1.0 | 1.0 | 1.0 |
| 2 | 132 | 156 | 1.29 (0.90 to 1.85) | 1.27 (0.89 to 1.81) | 1.29 (1.00 to 1.65) | |
| 3 | 130 | 156 | 1.35 (0.93 to 1.96) | 1.35 (0.93 to 1.97) | 1.35 (1.04 to 1.76) | |
| 4 | 160 | 156 | 1.70 (1.18 to 2.45) | 1.50 (1.01 to 2.21) | 1.62 (1.25 to 2.11) | |
| Ptrend† | .006 | .05 | <.001 | |||
| IL-1RA | 1 | 374 | 462 | 1.0 | 1.0 | 1.0 |
| 2 | 79 | 81 | 1.10 (0.77 to 1.59) | 0.71 (0.51 to 1.00) | 0.92 (0.74 to 1.14) | |
| 3 | 72 | 82 | 1.09 (0.75 to 1.58) | ‡ | ‡ | |
| Ptrend†/P | .57 | .05 | .44 | |||
| IL-7 | 1 | 223 | 258 | 1.0 | 1.0 | 1.0 |
| 2 | 89 | 122 | 0.98 (0.69 to 1.39) | 1.47 (1.05 to 2.06) | 1.17 (0.95 to 1.44) | |
| 3 | 102 | 123 | 1.00 (0.70 to 1.42) | ‡ | ‡ | |
| 4 | 111 | 122 | 1.14 (0.80 to 1.63) | ‡ | ‡ | |
| Ptrend†/P | .52 | .02 | .15 | |||
| TGF-A | 1 | 118 | 158 | 1.0 | 1.0 | 1.0 |
| 2 | 106 | 154 | 1.05 (0.73 to 1.52) | 1.26 (0.86 to 1.84) | 1.14 (0.88 to 1.48) | |
| 3 | 173 | 157 | 1.55 (1.09 to 2.22) | 1.40 (0.96 to 2.05) | 1.47 (1.14 to 1.90) | |
| 4 | 128 | 156 | 1.12 (0.77 to 1.63) | 1.56 (1.07 to 2.27) | 1.31 (1.01 to 1.71) | |
| Ptrend† | .22 | .02 | .01 | |||
| CXCL5/ENA 78 | 1 | 118 | 156 | 1.0 | 1.0 | 1.0 |
| 2 | 129 | 156 | 0.99 (0.69 to 1.41) | 1.43 (1.01 to 2.03) | 1.21 (0.94 to 1.54) | |
| 3 | 142 | 157 | 1.20 (0.83 to 1.72) | 1.13 (0.79 to 1.63) | 1.17 (0.91 to 1.51) | |
| 4 | 136 | 156 | 0.96 (0.96 to 1.43) | 1.68 (1.15 to 2.45) | 1.29 (0.98 to 1.68) | |
| Ptrend† | .87 | .03 | .10 | |||
| CXCL9/MIG | 1 | 97 | 156 | 1.0 | 1.0 | 1.0 |
| 2 | 108 | 156 | 1.14 (0.78 to 1.67) | 0.92 (0.63 to 1.34) | 1.02 (0.79 to 1.33) | |
| 3 | 135 | 157 | 1.44 (0.98 to 2.11) | 1.38 (0.95 to 2.00) | 1.40 (1.08 to 1.83) | |
| 4 | 185 | 156 | 2.09 (1.41 to 3.08) | 1.63 (1.12 to 2.36) | 1.82 (1.40 to 2.37) | |
| Ptrend† | <.001 | .003 | <.001 | |||
| CXCL13/BCA-1 | 1 | 115 | 151 | 1.0 | 1.0 | 1.0 |
| 2 | 116 | 152 | 0.91 (0.63 to 1.31) | 0.97 (0.67 to 1.40) | 0.95 (0.73 to 1.23) | |
| 3 | 133 | 152 | 1.08 (0.76 to 1.53) | 0.99 (0.68 to 1.45) | 1.06 (0.82 to 1.37) | |
| 4 | 145 | 152 | 1.21 (0.85 to 1.74) | 1.59 (1.10 to 2.29) | 1.40 (1.08 to 1.80) | |
| Ptrend† | .20 | .01 | .005 | |||
| CCL17/TARC | 1 | 120 | 156 | 1.0 | 1.0 | 1.0 |
| 2 | 102 | 156 | 0.73 (0.50 to 1.07) | 1.16 (0.80 to 1.67) | 0.93 (0.72 to 1.21) | |
| 3 | 113 | 157 | 0.76 (0.53 to 1.11) | 1.09 (0.76 to 1.57) | 0.91 (0.71 to 1.18) | |
| 4 | 190 | 156 | 1.26 (0.89 to 1.78) | 1.50 (1.06 to 2.13) | 1.38 (1.08 to 1.76) | |
| Ptrend† | .13 | .03 | .01 | |||
| CCL22/MDC | 1 | 143 | 156 | 1.0 | 1.0 | 1.0 |
| 2 | 110 | 156 | 0.80 (0.56 to 1.14) | 1.13 (0.78 to 1.65) | 0.93 (0.72 to 1.19) | |
| 3 | 98 | 157 | 0.68 (0.48 to 0.97) | 0.96 (0.66 to 1.41) | 0.80 (0.62 to 1.04) | |
| 4 | 174 | 156 | 1.13 (0.79 to 1.60) | 1.72 (1.18 to 2.50) | 1.38 (1.07 to 1.78) | |
| Ptrend† | .70 | .009 | .03 | |||
* Odds ratios and 95% confidence intervals were estimated in conditional logistic regression models. Models were adjusted for matching criteria, personal history of bronchitis/emphysema, history of coronary heart disease or heart attack, family history of lung cancer, use of aspirin/ibuprofen, body mass index, race, and education. BCA = B-cell attracting chemokine; CI = confidence interval; CXCL9/MIG = monokine induced by gamma interferon; CRP = C-reactive protein; ENA = epithelial-derived neutrophil-activating peptide; IL = interleukin; MDC = macrophage-derived chemokine; OR = odds ratio; SAA = serum amyloid A; sTNFRII = soluble tumor necrosis factor receptor-2; TARC = thymus- and activation-regulated chemokine; TGF = transforming growth factor-alpha.
† Two-sided Ptrend values across marker categories were assessed with the Wald test using marker levels as an ordinal variable with 1 degree of freedom.
‡ For IL-7 and IL-1Ra, the fraction of values above the lowest limit of quantification (LLOQ) was greater in the replication study than in the discovery study. Therefore, more categories were created for the replication study, while these markers were classified as above or below the LLOQ in the discovery study and the pooled analysis.