Background
Materials and methods
Study subjects and sample data collection
SNP selection and genotyping
Statistical analysis
Results
Baseline characteristics
Variable | Case (%) (434) | Control (%) (593) | P value |
---|---|---|---|
Age, year (mean ± SD) | 57.97 ± 11.85 | 56.67 ± 15.88 | 0.134 |
Age, (year) | |||
≤ 57 | 190 (43.8) | 264 (44.5) | 0.813 |
> 57 | 244 (56.2) | 329 (55.5) | |
Gender | |||
Male | 111 (25.6) | 180 (30.4) | 0.093 |
Female | 323 (74.4) | 413 (69.6) | |
Smoking status | |||
Never | 338 (77.9) | 475 (80.1) | 0.044a |
Ever | 96 (22.1) | 118 (19.9) | |
Clinical stage | |||
I, II | 86 (19.8) | ||
III | 198 (45.6) | ||
IV | 59 (13.6) | ||
Other | 91 (21.0) | ||
Histology | |||
AD | 233 (53.6) | ||
SQ | 89 (20.5) | ||
SCLC | 61 (14.1) | ||
Other | 51 (11.8) |
Genotype distribution and lung cancer susceptibility
Genotype | Controls (%) (593) | Lung cancer | Non-small cell lung cancer | ||||
---|---|---|---|---|---|---|---|
Cases (%) (434) | ORa (95% CI) | P value | Cases (%)(331) | ORa (95% CI) | P value | ||
Rs4848320 | |||||||
CC (ref) | 402 (67.8) | 291 (67.1) | 1.00 (ref) | 220 (66.5) | 1.00 (ref) | ||
CT | 175 (29.5) | 131 (30.2) | 1.036 (0.788–1.362) | 0.800 | 101 (30.5) | 1.160 (0.787–1.427) | 0.703 |
TT | 16 (2.7) | 12 (2.8) | 1.041 (0.482–2.247) | 0.918 | 10 (3.0) | 1.168 (0.515–2.647) | 0.710 |
CT + TT vs CC | 1.036 (0.795–1.352) | 0.792 | 1.069 (0.801–1.426) | 0.653 | |||
TT vs CT + CC | 1.030 (0.479–2.212) | 0.940 | 1.147 (0.509–2.586) | 0.741 | |||
Rs1110839 | |||||||
TT (ref) | 250 (42.2) | 174 (40.1) | 1.00 (ref) | 134 (40.5) | 1.00 (ref) | ||
TG | 274 (46.2) | 209 (48.2) | 1.083 (0.830–1.413) | 0.559 | 158 (47.7) | 1.068 (0.799–1.428) | 0.656 |
GG | 69 (11.6) | 51 (11.8) | 1.079 (0.714–1.632) | 0.717 | 39 (11.8) | 1.066 (0.679–1.672) | 0.782 |
TG + GG vs TT | 1.082 (0.839–1.394) | 0.543 | 1.068 (0.810–1.407) | 0.642 | |||
GG vs TG + TT | 1.034 (0.702–1.525) | 0.864 | 1.029 (0.674–1.570) | 0.895 |
Genotype | Controls (%) (593) | Lung adenocarcinoma | Squamous cell carcinoma | ||||
---|---|---|---|---|---|---|---|
Cases (%) (233) | ORa (95 %CI) | P value | Cases (%) (89) | ORa (95% CI) | P value | ||
Rs4848320 | |||||||
CC (ref) | 402 (67.8) | 159 (68.2) | 1.00 (ref) | 58 (65.2) | 1.00 (ref) | ||
CT | 175 (29.5) | 68 (29.2) | 0.957 (0.679–1.350) | 0.804 | 28 (31.5) | 1.127 (0.690–1.840) | 0.634 |
TT | 16 (2.7) | 6 (2.6) | 0.910 (0.343–2.413) | 0.849 | 3 (3.4) | 1.230 (0.339–4.466) | 0.753 |
CT + TT vs CC | 0.953 (0.683–1.331) | 0.779 | 1.135 (0.706–1.826) | 0.600 | |||
TT vs CT + CC | 0.922 (0.350–2.431) | 0.870 | 1.184 (0.329–4.259) | 0.796 | |||
Rs1110839 | |||||||
TT (ref) | 250 (42.2) | 102 (43.8) | 1.00 (ref) | 30 (33.7) | 1.00 (ref) | ||
TG | 274 (46.2) | 107 (45.9) | 0.960 (0.691–1.334) | 0.808 | 46 (51.7) | 1.336 (0.813–2.195) | 0.253 |
GG | 69 (11.6) | 24 (10.3) | 0.805 (0.474–1.368) | 0.423 | 13 (14.6) | 1.605 (0.787–3.273) | 0.193 |
TG + GG vs TT | 0.928 (0.678–1.270) | 0.639 | 1.388 (0.864–2.229) | 0.175 | |||
GG vs TG + TT | 0.822 (0.498–1.359) | 0.445 | 1.362 (0.712–2.608) | 0.350 |
Variant | Controls (%) (593) | Lung cancer | Non-small cell lung cancer | ||||
---|---|---|---|---|---|---|---|
Cases (%) (434) | ORa (95% CI) | P value | Cases (%) (331) | ORa (95% CI) | P value | ||
No. of alleles | |||||||
0 (ref) | 232 (39.1) | 168 (38.7) | 1.00 (ref) | 129 (39.0) | 1.00 (ref) | ||
1 | 174 (29.3) | 115 (26.5) | 0.893 (0.654–1.218) | 0.474 | 85 (25.7) | 0.871 (0.619–1.225) | 0.427 |
2 | 132 (22.3) | 112 (25.8) | 1.167 (0.846–1.612) | 0.346 | 88 (26.6) | 1.207 (0.852–1.710) | 0.291 |
3–4 | 55 (9.3) | 39 (9.0) | 0.985 (0.622–1.560) | 0.948 | 29 (8.8) | 0.947 (0.572–1.569) | 0.833 |
Trend | Pb = 0.893 | Pb = 0.964 | |||||
0 | 232 (39.1) | 168 (38.7) | 1.00 (ref) | 129 (39.0) | 1.00 (ref) | ||
1–4 | 361 (60.9) | 266 (61.3) | 1.007 (0.780–1.301) | 0.955 | 202 (61.0) | 1.005 (0.761–1.328) | 0.971 |
SNP | Genotype | Smoking exposure | Controls (%) | Cases (%) | ORª (95% CI) | P value |
---|---|---|---|---|---|---|
Rs4848320 | CC | Ever | 88 (74.6) | 58 (60.4) | 1.00 (ref) | |
CT | 29 (24.6) | 32 (33.3) | 1.695 (0.922–3.119) | 0.090 | ||
TT | 1 (0.8) | 6 (6.3) | 8.219 (0.957–70.618) | 0.055 | ||
CT + TT vs CC | 1.929 (1.070–3.479) | 0.029 | ||||
TT vs CT + CC | 7.048 (0.827–60.092) | 0.074 | ||||
CC | Never | 314 (66.1) | 233 (68.9) | 1.00 (ref) | ||
CT | 146 (30.7) | 99 (29.3) | 0.914 (0.671–1.245) | 0.568 | ||
TT | 15 (3.2) | 6 (1.8) | 0.563 (0.213–1.484) | 0.245 | ||
CT + TT vs CC | 0.882 (0.653–1.192) | 0.415 | ||||
TT vs CT + CC | 0.578 (0.220–1.519) | 0.266 | ||||
Rs1110839 | TT | Ever | 50 (42.4) | 30 (31.3) | 1.00 (ref) | |
TG | 62 (52.5) | 53 (55.2) | 1.376 (0.763–2.482) | 0.288 | ||
GG | 6 (5.1) | 13 (13.5) | 3.224 (1.089–9.544) | 0.034 | ||
TG + GG vs TT | 1.539 (0.867–2.731) | 0.141 | ||||
GG vs TG + TT | 2.652 (0.954–7.371) | 0.062 | ||||
TT | Never | 200 (42.1) | 144 (42.6) | 1.00 (ref) | ||
TG | 212 (44.6) | 156 (46.2) | 1.010 (0.748–1.364) | 0.950 | ||
GG | 63 (13.3) | 38 (11.2) | 0.847 (0.534–1.341) | 0.478 | ||
TG + GG vs TT | 0.973 (0.731–1.294) | 0.849 | ||||
GG vs TG + TT | 0.842 (0.546–1.299) | 0.437 |
SNP | Genotype | Gender | Controls (%) | Cases (%) | ORª (95% CI) | P value |
---|---|---|---|---|---|---|
Rs4848320 | CC | Male | 124 (68.9) | 69 (62.2) | 1.00 (ref) | |
CT | 51 (28.3) | 37 (33.3) | 1.334 (0.774–2.298) | 0.299 | ||
TT | 5 (2.8) | 5 (4.5) | 2.042 (0.500–8.333) | 0.320 | ||
CT + TT vs CC | 1.389 (0.821–2.350) | 0.220 | ||||
TT vs CT + CC | 1.860 (0.461–7.498) | 0.383 | ||||
CC | Female | 278 (67.3) | 222 (68.7) | 1.00 (ref) | ||
CT | 124 (30.0) | 94 (29.1) | 0.959 (0.695–1.323) | 0.797 | ||
TT | 11 (2.7) | 7 (2.2) | 0.824 (0.313–2.166) | 0.694 | ||
CT + TT vs CC | 0.948 (0.693–1.297) | 0.737 | ||||
TT vs CT + CC | 0.835 (0.319–2.183) | 0.713 | ||||
Rs1110839 | TT | Male | 79 (43.9) | 32 (28.8) | 1.00 (ref) | |
TG | 84 (46.7) | 60 (54.1) | 1.582 (0.908–2.757) | 0.105 | ||
GG | 17 (9.4) | 19 (17.1) | 3.096 (1.343–7.134) | 0.008 | ||
TG + GG vs TT | 1.804 (1.061–3.067) | 0.029 | ||||
GG vs TG + TT | 2.376 (1.102–5.121) | 0.027 | ||||
TT | Female | 171 (41.4) | 142 (44.0) | 1.00 (ref) | ||
TG | 190 (46.0) | 149 (46.1) | 0.957 (0.702–1.305) | 0.783 | ||
GG | 52 (12.6) | 32 (9.9) | 0.751 (0.457–1.233) | 0.258 | ||
TG + GG vs TT | 0.913 (0.680–1.228) | 0.548 | ||||
GG vs TG + TT | 0.768 (0.481–1.228) | 0.271 |
SNP | Genotype | Age | Controls (%) | Cases (%) | ORª (95% CI) | P value |
---|---|---|---|---|---|---|
Rs4848320 | CC | ≤ 57 | 180 (68.2) | 132 (69.5) | 1.00 (ref) | |
CT | 78 (29.5) | 54 (28.4) | 0.852 (0.548–1.324) | 0.476 | ||
TT | 6 (2.3) | 4 (2.1) | 1.323 (0.319–5.496) | 0.700 | ||
CT + TT vs CC | 0.876 (0.570–1.347) | 0.547 | ||||
TT vs CT + CC | 1.385 (0.336–5.716) | 0.652 | ||||
CC | > 57 | 222 (67.5) | 159 (65.2) | 1.00 (ref) | ||
CT | 97 (29.5) | 77 (31.6) | 1.109 (0.768–1.602) | 0.581 | ||
TT | 15 (3.0) | 8 (3.3) | 1.214 (0.462–3.189) | 0.694 | ||
CT + TT vs CC | 1.119 (0.784–1.596) | 0.537 | ||||
TT vs CT + CC | 1.175 (0.451–3.066) | 0.741 | ||||
Rs1110839 | TT | ≤ 57 | 115 (43.6) | 85 (44.7) | 1.00 (ref) | |
TG | 123 (46.6) | 86 (45.3) | 0.943 (0.621–1.434) | 0.784 | ||
GG | 26 (9.8) | 19 (10.0) | 1.288 (0.633–2.620) | 0.486 | ||
TG + GG vs TT | 0.994 (0.666–1.484) | 0.976 | ||||
GG vs TG + TT | 1.327 (0.674–2.612) | 0.413 | ||||
TT | > 57 | 135 (40.1) | 89 (36.5) | 1.00 (ref) | ||
TG | 151 (45.9) | 123 (50.4) | 1.299 (0.902–1.872) | 0.160 | ||
GG | 43 (13.1) | 32 (13.1) | 1.195 (0.698–2.048) | 0.516 | ||
TG + GG vs TT | 1.276 (0.902–1.806) | 0.169 | ||||
GG vs TG + TT | 1.034 (0.628–1.703) | 0.894 |
Interaction between SNPs and smoking exposure
SNPs | Genotype | Smoking exposure | Controls (%) | Cases (%) | ORa (95% CI) | P value |
---|---|---|---|---|---|---|
Rs4848320 | CC | Never | 314 (53.0) | 233 (53.7) | 1 (ref) | |
CT + TT | Never | 161 (27.2) | 105 (24.2) | 0.875 (0.648–1.182) | 0.384 | |
CC | Ever | 88 (14.8) | 58 (13.4) | 1.129 (0.738–1.728) | 0.576 | |
CT + TT | Ever | 30 (5.1) | 85 (31.8) | 2.218 (1.272–3.869) | 0.005 | |
Rs1110839 | TT | Never | 200 (33.7) | 144 (33.2) | 1 (ref) | |
TG + GG | Never | 275 (46.4) | 194 (44.7) | 0.968 (0.729–1.286) | 0.822 | |
TT | Ever | 50 (8.4) | 30 (6.9) | 1.043 (0.611–1.782) | 0.877 | |
TG + GG | Ever | 68 (11.5) | 66 (15.2) | 1.755 (1.108–2.781) | 0.017 |
Measure | Rs4848320 | Rs1110839 | ||
---|---|---|---|---|
Estimate | 95% CI | Estimate | 95% CI | |
RERI | 0.940 | 0.045–1.835 | 0.535 | − 0.092–1.162 |
AP | 0.551 | 0.231–0.870 | 0.397 | − 0.007–0.801 |
S | − 3.306 | #NUM! | − 1.862 | #NUM! |
SNPs | Variables | ORa (95% CI) | P value |
---|---|---|---|
Rs4848320 | Smoking exposure | 0.503 (0.196–1.292) | 0.153 |
Rs4848320 CT + TT | 0.875 (0.648–1.182) | 0.384 | |
Interaction | 2.244 (1.162–4.334) | 0.016 | |
Rs1110839 | Smoking exposure | 0.600 (0.202–1.783) | 0.358 |
Rs1110839 TG + GG | 0.968 (0.729–1.286) | 0.822 | |
Interaction | 1.738 (0.920–3.285) | 0.089 |