Table 3.
Codominant, dominant, recessive, allelic and other genetic models for PD1.3 G>A, PD1.5 C>T, PD1.7 G>A and PD-L1 +8293 C>A estimated through the modified Poisson regression analysis
| Genotypic model | irAE |
Non-irAE |
Total | Relative risk of irAEs |
||||
|---|---|---|---|---|---|---|---|---|
| No. | % | No. | % | RR | 95% CL | P value | ||
| PD1.3 G>A (rs11568821) | ||||||||
| Codominant | 0.001 | |||||||
| G/G | 34 | 37.0 | 58 | 63.0 | 92 | 1.00 | (Ref.) | |
| G/A | 14 | 43.8 | 18 | 56.3 | 32 | 1.35 | 0.76-2.41 | |
| A/A | 1 | 100.0 | 0 | 0.0 | 1 | 3.94 | 1.90-8.18 | |
| Dominant | 0.207 | |||||||
| G/G | 34 | 37.0 | 58 | 63.0 | 92 | 1.00 | (Ref.) | |
| G/A + A/A | 15 | 45.5 | 18 | 54.5 | 33 | 1.43 | 0.81-2.50 | |
| Recessive | <0.001 | |||||||
| G/A+G/G | 48 | 38.7 | 76 | 61.3 | 124 | 1.00 | (Ref.) | |
| A/A | 1 | 100.0 | 0 | 0.0 | 1 | 3.61 | 1.82-7.16 | |
| Allelic | 0.157 | |||||||
| G | 82 | 38.0 | 134 | 62.0 | 216 | 1.00 | (Ref.) | |
| A | 16 | 47.1 | 18 | 52.9 | 34 | 1.41 | 0.88-2.27 | |
| Heterozygous versus homozygous | 0.308 | |||||||
| G/G | 34 | 37.0 | 58 | 63.0 | 92 | 1.00 | (Ref.) | |
| G/A | 14 | 43.8 | 18 | 56.3 | 32 | 1.35 | 0.76-2.41 | |
| PD1.5 C>T (rs2227981) | ||||||||
| Codominant | 0.170 | |||||||
| C/C | 23 | 45.1 | 28 | 54.9 | 51 | 1.00 | (Ref.) | |
| C/T | 24 | 39.3 | 37 | 60.7 | 61 | 0.75 | 0.48-1.18 | |
| T/T | 2 | 15.4 | 11 | 84.6 | 13 | 0.32 | 0.08-1.24 | |
| Dominant | 0.088 | |||||||
| C/C | 23 | 45.1 | 28 | 54.9 | 51 | 1.00 | (Ref.) | |
| C/T + T/T | 26 | 35.1 | 48 | 64.9 | 74 | 0.67 | 0.43-1.06 | |
| Recessive | 0.144 | |||||||
| C/C+C/T | 47 | 42.0 | 65 | 58.0 | 112 | 1.00 | (Ref.) | |
| T/T | 2 | 15.4 | 11 | 84.6 | 13 | 0.37 | 0.10-1.39 | |
| Allelic | 0.058 | |||||||
| C | 70 | 42.9 | 93 | 57.1 | 163 | 1.00 | (Ref.) | |
| T | 28 | 32.2 | 59 | 67.8 | 87 | 0.70 | 0.48-1.01 | |
| Homozygous | 0.253 | |||||||
| C/C | 23 | 45.1 | 28 | 54.9 | 51 | 1.00 | (Ref.) | |
| T/T | 2 | 15.4 | 11 | 84.6 | 13 | 0.44 | 0.11-1.79 | |
| Heterozygous versus homozygous | 0.166 | |||||||
| C/C | 23 | 45.1 | 28 | 54.9 | 51 | 1.00 | (Ref.) | |
| C/T | 24 | 39.3 | 37 | 60.7 | 61 | 0.73 | 0.47-1.14 | |
| PD1.7 T>C (rs7421861) | ||||||||
| Codominant | 0.283 | |||||||
| T/T | 26 | 44.1 | 33 | 55.9 | 59 | 1.00 | (Ref.) | |
| T/C | 20 | 41.7 | 28 | 58.3 | 48 | 1.04 | 0.64-1.69 | |
| C/C | 3 | 16.7 | 15 | 83.3 | 18 | 0.35 | 0.09-1.31 | |
| Dominant | 0.610 | |||||||
| T/T | 26 | 44.1 | 33 | 55.9 | 59 | 1.00 | (Ref.) | |
| T/C + C/C | 23 | 34.8 | 43 | 65.2 | 66 | 0.88 | 0.54-1.43 | |
| Recessive | 0.112 | |||||||
| T/C+T/T | 46 | 43.0 | 61 | 57.0 | 107 | 1.00 | (Ref.) | |
| C/C | 3 | 16.7 | 15 | 83.3 | 18 | 0.35 | 0.09-1.28 | |
| Allelic | 0.206 | |||||||
| T | 72 | 43.4 | 94 | 56.6 | 166 | 1.00 | (Ref.) | |
| C | 26 | 31.0 | 58 | 69.0 | 84 | 0.77 | 0.51-1.15 | |
| Homozygous | 0.082 | |||||||
| T/T | 26 | 44.1 | 33 | 55.9 | 59 | 1.00 | (Ref.) | |
| C/C | 3 | 16.7 | 15 | 83.3 | 18 | 0.33 | 0.09-1.15 | |
| PD-L1 +8293 C>A (rs2890658) | ||||||||
| Codominant | 0.079 | |||||||
| C/C | 40 | 46.0 | 47 | 54.0 | 87 | 1.00 | (Ref.) | |
| C/A | 8 | 22.2 | 28 | 77.8 | 36 | 0.45 | 0.22-0.93 | |
| A/A | 1 | 50.0 | 1 | 50.0 | 2 | 1.37 | 0.28-6.69 | |
| Dominant | 0.045 | |||||||
| C/C | 40 | 46.0 | 47 | 54.0 | 87 | 1.00 | (Ref.) | |
| C/A + A/A | 9 | 23.7 | 29 | 76.3 | 38 | 0.50 | 0.25-0.98 | |
| Recessive | 0.563 | |||||||
| C/C + C/A | 48 | 39.0 | 75 | 61.0 | 123 | 1.00 | (Ref.) | |
| A/A | 1 | 50.0 | 1 | 50.0 | 2 | 1.60 | 0.38-7.80 | |
| Allelic | 0.100 | |||||||
| C | 88 | 41.9 | 122 | 58.1 | 210 | 1.00 | (Ref.) | |
| A | 10 | 25.0 | 30 | 75.0 | 40 | 0.59 | 0.32-1.10 | |
| Heterozygous versus homozygous | 0.031 | |||||||
| C/C | 40 | 46.0 | 47 | 54.0 | 87 | 1.00 | (Ref.) | |
| C/A | 8 | 22.2 | 28 | 77.8 | 36 | 0.45 | 0.22-0.93 | |
| Total | 49 | 39 | 76 | 61 | 125 | — | — | — |
P value: probability level associated with the likelihood ratio test result.
95% CL, 95% confidence limits for RR; irAEs, immune-related adverse events; Ref., reference category; RR, (risk ratio) irAE relative frequency in each SNV genotype in comparison to the irAE relative frequency in the reference genotype, adjusted for baseline age, gender, Eastern Oncology Cooperative Group performance status (ECOG PS), lactate dehydrogenase (LDH) levels, number of metastatic sites at first and brain metastases; SNV, single nucleotide variant.