Table 2.
Association between methylation-predicted immune cell profiles and risk of total lung cancer and NSCLC risk, overall and stratified by time to diagnosis, case–control study nested in the CLUE I/II cohort
| All lung cancersa OR (95% CI) |
Non-small cell lung cancerb OR (95% CI) |
|
|---|---|---|
| mdNLRc | 1.11 (0.89, 1.38) | 1.47 (1.08, 2.02) |
| Time to diagnosis ≤ 10 years | 0.97 (0.69, 1.35) | 1.41 (0.90, 2.20) |
| Time to diagnosis > 10 years | 1.22 (0.91, 1.64) | 1.57 (0.98, 2.49) |
| CD4/CD8 Ratioc | 1.17 (0.80, 1.72) | 1.16 (0.74, 1.82) |
| Time to diagnosis ≤ 10 years | 0.94 (0.56, 1.57) | 0.79 (0.38, 1.66) |
| Time to diagnosis > 10 years | 1.47 (0.82, 2.62) | 1.72 (0.77, 3.85) |
| B cell/lymphocyte ratioc | 1.07 (0.73, 1.57) | 0.94 (0.58, 1.52) |
| Time to diagnosis ≤ 10 years | 1.16 (0.63, 2.14) | 0.91 (0.42, 1.97) |
| Time to diagnosis > 10 years | 0.98 (0.60, 1.59) | 0.93 (0.50, 1.71) |
| T cell/lymphocyte ratioc | 1.06 (0.72, 1.56) | 0.94 (0.60, 1.48) |
| Time to diagnosis ≤ 10 years | 1.11 (0.62, 1.98) | 1.03 (0.49, 2.16) |
| Time to diagnosis > 10 years | 1.05 (0.63, 1.76) | 0.88 (0.48, 1.62) |
| Monocyte/lymphocyte ratioc | 1.15 (0.78, 1.69) | 1.65 (0.99, 2.76) |
| Time to diagnosis ≤ 10 years | 1.18 (0.66, 2.11) | 1.62 (0.75, 3.51) |
| Time to diagnosis > 10 years | 1.16 (0.69, 1.94) | 1.81 (0.86, 3.80) |
| (Neutrophil + monocyte)/lymphocyte ratioc | 1.13 (0.79, 1.61) | 1.46 (0.87, 2.44) |
| Time to diagnosis ≤ 10 years | 0.96 (0.59, 1.56) | 1.32 (0.67, 2.60) |
| Time to diagnosis > 10 years | 1.26 (0.78, 2.04) | 1.62 (0.80, 3.29) |
| Eosinophil/lymphocyte ratioc | 0.94 (0.64, 1.38) | 0.89 (0.53, 1.49) |
| Time to diagnosis ≤ 10 years | 0.81 (0.44, 1.49) | 1.21 (0.48, 3.08) |
| Time to diagnosis > 10 years | 1.01 (0.64, 1.59) | 0.73 (0.36, 1.48) |
| CD4 naïve/lymphocyte ratioc | 1.22 (0.83, 1.80) | 1.36 (0.84, 2.20) |
| Time to diagnosis ≤ 10 years | 1.47 (0.72, 2.99) | 1.70 (0.74, 3.93) |
| Time to diagnosis > 10 years | 1.11 (0.68, 1.80) | 1.19 (0.67, 2.12) |
| B cell/CD8 ratioc | 0.97 (0.68, 1.38) | 1.00 (0.66, 1.52) |
| Time to diagnosis ≤ 10 years | 1.06 (0.61, 1.83) | 1.11 (0.58, 2.11) |
| Time to diagnosis > 10 years | 0.85 (0.45, 1.62) | 0.90 (0.44, 1.83) |
| CD8/treg ratioc | 0.81 (0.55, 1.19) | 0.73 (0.45, 1.18) |
| Time to diagnosis ≤ 10 years | 0.86 (0.47, 1.59) | 0.72 (0.33, 1.56) |
| Time to diagnosis > 10 years | 0.78 (0.45, 1.35) | 0.68 (0.33, 1.38) |
| Treg > 0 versus Treg = 0c | 1.05 (0.74, 1.50) | 1.07 (0.70, 1.63) |
| Time to diagnosis ≤ 10 years | 0.95 (0.53, 1.70) | 1.12 (0.55, 2.27) |
| Time to diagnosis > 10 years | 1.10 (0.70, 1.73) | 1.06 (0.61, 1.83) |
| B cell naïve/B cell memory ratioc | 0.85 (0.58, 1.25) | 0.87 (0.57, 1.32) |
| Time to diagnosis ≤ 10 years | 0.65 (0.24, 1.76) | 0.65 (0.21, 2.01) |
| Time to diagnosis > 10 years | 0.93 (0.56, 1.56) | 0.96 (0.56, 1.66) |
| CD4 naïve/CD4 memory ratioc | 1.04 (0.73, 1.48) | 1.59 (0.81, 3.13) |
| Time to diagnosis ≤ 10 years | 0.98 (0.59, 1.64) | 2.67 (0.65, 11.01) |
| Time to diagnosis > 10 years | 1.18 (0.60, 2.32) | 1.34 (0.58, 3.10) |
| CD8 naïve/CD8 memory ratioc | 0.99 (0.72, 1.37) | 1.01 (0.53, 1.92) |
| Time to diagnosis ≤ 10 years | 0.66 (0.15, 2.81) | 0.74 (0.17, 3.15) |
| Time to diagnosis > 10 years | 1.04 (0.71, 1.53) | 1.73 (0.36, 8.38) |
Bold OR and CI values indicate statistical significance. Underline OR and CI values indicate borderline statistical significance after multiple comparison adjustment
a208 cases and 208 controls matched on age at blood draw, sex, smoking status, and model further adjusting for BMI, surrogate variables for batch effects, and a methylation-predicted pack-years smoked
b150 cases and 150 controls matched on age at blood draw, sex, smoking status, and model further adjusting for BMI, surrogate variables for batch effects, and a methylation-predicted pack-years smoked
cOR results reported per 1 unit SD increase (mdNLR SD: 1.16; CD4/CD8 ratio SD: 2.07; BL ratio SD: 0.0526; TL ratio SD: 0.0802; ML ratio SD: 0.118; NM/L ratio SD: 1.22; EL ratio SD: 0.0722; CD4nv/L ratio SD: 0.0915; B/CD8 ratio SD: 3.07; CD8/Treg ratio SD: 115; Bnv/Bmem ratio SD: 109; CD4nv/CD4mem ratio SD: 0.429; CD8nv/CD8mem ratio SD: 2.05) and OR results reported for Treg > 0 versus 0; Bonferroni-adjusted CI reported for all except mdNLR (a prior hypothesis)