Introduction
Methods
Subjects
Genotyping
Statistical data
Results
Subjects characteristics
Variable | Cases (688) | Control (690) | p | |
---|---|---|---|---|
Age | Mean ± SD, years | 59.78 ± 11.29 | 59.62 ± 9.55 | 0.774 |
> 60years | 353 (51.3%) | 380 (55.1%) | ||
≤ 60 years | 335 (48.7%) | 310 (44.9%) | ||
Gender | 0.964 | |||
Male | 402 (58.4%) | 404 (58.6%) | ||
Female | 286 (41.6%) | 286 (41.4%) | ||
Smoking | 0.624 | |||
Yes | 312 (45.3%) | 322 (46.7%) | ||
No | 376 (54.7%) | 368 (53.3%) | ||
Drinking | 0.828 | |||
Yes | 330 (48.0%) | 335 (48.6%) | ||
No | 358 (52.0%) | 355 (51.4%) | ||
BMI | < 0.001 | |||
> 24 kg/m2 | 150 (33.0%) | 216 (51.2%) | ||
≤ 24 kg/m2 | 304 (67.0%) | 206 (48.8%) | ||
Lymph nodes metastasis | ||||
Yes | 183 (26.6%) | |||
No | 53 (7.7%) | |||
Unavailable | 452 (65.7%) | |||
Pathological type | ||||
Colon cancer | 320 (46.5%) | |||
Rectal cancer | 368 (53.5%) | |||
Stage | ||||
I-II | 109 (15.8%) | |||
III-IV | 263 (38.2%) | |||
Unavailable | 316 (45.9%) |
Relationship of selected variants with CRC risk
SNP ID | Chr: Position | Alleles (Ref/Alt) | MAF | HWE | Call rate | OR (95% CI) | p | Exon | dbSNP func annot | Haploreg4.1 | RegulomeDB | P-Value for eQTL in Blood | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Cases | Controls | O(HET) | E(HET) | p | |||||||||||
rs3740938 | 11:102716331 | A/G | 0.257 | 0.218 | 0.326 | 0.341 | 0.264 | 99.8% | 1.24 (1.04–1.48) | 0.016* | 6 | Synonymous L (Leu) > L (Leu) | Promoter histone marks; Enhancer histone marks; Motifs changed | other | 0.027 |
rs1940475 | 11:102722517 | T/C | 0.393 | 0.367 | 0.454 | 0.465 | 0.514 | 100.0% | 1.12 (0.96–1.30) | 0.163 | 2 | Missense K (Lys) > E (Glu) | Enhancer histone marks; DNAse; Motifs changed | eQTL/caQTL + TF binding / chromatin accessibility peak | 2.720e-13 |
rs3765620 | 11:102724761 | G/A | 0.386 | 0.359 | 0.448 | 0.460 | 0.508 | 99.8% | 1.13 (0.96–1.31) | 0.134 | 1 | Missense T (Thr) > I (Ile) | Enhancer histone marks; DNAse; Motifs changed | other | 1.620e-12 |
SNP ID | Model | Genotype | Control | Case | OR (95% CI) | p |
---|---|---|---|---|---|---|
rs3740938 | Codominant | GG | 427 (61.9%) | 379 (55.2%) | 1 | 0.044* |
GA | 225 (32.6%) | 261 (38%) | 1.31 (1.04–1.64) | |||
AA | 38 (5.5%) | 46 (6.7%) | 1.37 (0.87–2.15) | |||
Dominant | GG | 427 (61.9%) | 379 (55.2%) | 1 | 0.013* | |
GA-AA | 263 (38.1%) | 307 (44.8%) | 1.31 (1.06–1.63) | |||
Recessive | GG-GA | 652 (94.5%) | 640 (93.3%) | 1 | 0.350 | |
AA | 38 (5.5%) | 46 (6.7%) | 1.24 (0.79–1.93) | |||
Log-additive | --- | --- | --- | 1.24 (1.04–1.47) | 0.017* | |
rs1940475 | Codominant | CC | 280 (40.6%) | 261 (37.9%) | 1 | 0.360 |
CT | 313 (45.4%) | 313 (45.5%) | 1.08 (0.85–1.35) | |||
TT | 97 (14.1%) | 114 (16.6%) | 1.26 (0.92–1.74) | |||
Dominant | CC | 280 (40.6%) | 261 (37.9%) | 1 | 0.310 | |
CT-TT | 410 (59.4%) | 427 (62.1%) | 1.12 (0.90–1.39) | |||
Recessive | CC-CT | 593 (85.9%) | 574 (83.4%) | 1 | 0.200 | |
TT | 97 (14.1%) | 114 (16.6%) | 1.21 (0.90–1.63) | |||
Log-additive | --- | --- | --- | 1.11 (0.96–1.30) | 0.170 | |
rs3765620 | Codominant | A/A | 288 (41.7%) | 263 (38.3%) | 1 | 0.330 |
G/A | 309 (44.8%) | 316 (46.1%) | 1.12 (0.89–1.41) | |||
G/G | 93 (13.5%) | 107 (15.6%) | 1.26 (0.91–1.75) | |||
Dominant | A/A | 288 (41.7%) | 263 (38.3%) | 1 | 0.190 | |
G/A-G/G | 402 (58.3%) | 423 (61.7%) | 1.15 (0.93–1.43) | |||
Recessive | A/A-G/A | 597 (86.5%) | 579 (84.4%) | 1 | 0.270 | |
G/G | 93 (13.5%) | 107 (15.6%) | 1.19 (0.88–1.60) | |||
Log-additive | --- | --- | --- | 1.12 (0.96–1.31) | 0.140 |
Stratification analysis
Model | Genotype | Control | Case | OR (95% CI) | p -value | Control | Case | OR (95% CI) | p -value |
---|---|---|---|---|---|---|---|---|---|
Age stratification | Age > 60 years | Age ≤ 60 years | |||||||
Codominant | G/G | 239 (62.9%) | 191 (54.1%) | 1 | 0.045* | 188 (60.6%) | 188 (56.5%) | 1 | 0.210 |
G/A | 117 (30.8%) | 140 (39.7%) | 1.49 (1.09–2.05) | 108 (34.8%) | 121 (36.3%) | 1.14 (0.82–1.59) | |||
A/A | 24 (6.3%) | 22 (6.2%) | 1.17 (0.63–2.16) | 14 (4.5%) | 24 (7.2%) | 1.83 (0.91–3.67) | |||
Dominant | G/G | 239 (62.9%) | 191 (54.1%) | 1 | 0.018* | 188 (60.6%) | 188 (56.5%) | 1 | 0.230 |
G/A-A/A | 141 (37.1%) | 162 (45.9%) | 1.44 (1.06–1.94) | 122 (39.4%) | 145 (43.5%) | 1.22 (0.88–1.67) | |||
Recessive | G/G-G/A | 356 (93.7%) | 331 (93.8%) | 1 | 0.980 | 296 (95.5%) | 309 (92.8%) | 1 | 0.110 |
A/A | 24 (6.3%) | 22 (6.2%) | 1.01 (0.55–1.85) | 14 (4.5%) | 24 (7.2%) | 1.73 (0.87–3.44) | |||
Log-additive | --- | --- | --- | 1.26 (0.99–1.61) | 0.056 | --- | --- | 1.24 (0.95–1.61) | 0.110 |
Gender stratification | Males | Females | |||||||
Codominant | G/G | 235 (58.2%) | 217 (54.0%) | 1 | 0.450 | 192 (67.1%) | 162 (57.0%) | 1 | 0.048* |
G/A | 145 (35.9%) | 156 (38.8%) | 1.16 (0.86–1.55) | 80 (28.0%) | 105 (37.0%) | 1.55 (1.08–2.22) | |||
A/A | 24 (5.9%) | 29 (7.2%) | 1.33 (0.75–2.36) | 14 (4.9%) | 17 (6.0%) | 1.42 (0.68–2.99) | |||
Dominant | G/G | 235 (58.2%) | 217 (54.0%) | 1 | 0.240 | 192 (67.1%) | 162 (57.0%) | 1 | 0.014* |
G/A-A/A | 169 (41.8%) | 185 (46.0%) | 1.18 (0.89–1.56) | 94 (32.9%) | 122 (43.0%) | 1.53 (1.09–2.16) | |||
Recessive | G/G-G/A | 380 (94.1%) | 373 (92.8%) | 1 | 0.430 | 272 (95.1%) | 267 (94.0%) | 1 | 0.590 |
A/A | 24 (5.9%) | 29 (7.2%) | 1.25 (0.71–2.20) | 14 (4.9%) | 17 (6.0%) | 1.22 (0.59–2.54) | |||
Log-additive | --- | --- | --- | 1.16 (0.92–1.45) | 0.210 | --- | --- | 1.37 (1.03–1.81) | 0.027* |
BMI stratification | BMI > 24 kg/m2 | BMI ≤ 24 kg/m2 | |||||||
Codominant | G/G | 141 (65.3%) | 79 (52.7%) | 1 | 0.033* | 131 (63.6%) | 179 (59.1%) | 1 | 0.300 |
G/A | 65 (30.1%) | 59 (39.3%) | 1.67 (1.06–2.62) | 62 (30.1%) | 110 (36.3%) | 1.29 (0.88–1.90) | |||
A/A | 10 (4.6%) | 12 (8%) | 2.25 (0.92–5.48) | 13 (6.3%) | 14 (4.6%) | 0.78 (0.35–1.73) | |||
Dominant | G/G | 141 (65.3%) | 79 (52.7%) | 1 | 0.011* | 131 (63.6%) | 179 (59.1%) | 1 | 0.320 |
G/A-A/A | 75 (34.7%) | 71 (47.3%) | 1.74 (1.13–2.69) | 75 (36.4%) | 124 (40.9%) | 1.20 (0.83–1.74) | |||
Recessive | G/G-G/A | 206 (95.4%) | 138 (92.0%) | 1 | 0.170 | 193 (93.7%) | 289 (95.4%) | 1 | 0.400 |
A/A | 10 (4.6%) | 12 (80.0%) | 1.85 (0.77–4.42) | 13 (6.3%) | 14 (4.6%) | 0.72 (0.33–1.56) | |||
Log-additive | --- | --- | --- | 1.58 (1.11–2.24) | 0.010* | --- | --- | 1.08 (0.80–1.46) | 0.620 |
Smoking stratification | Smokers | Non-smokers | |||||||
Codominant | G/G | 206 (64.0%) | 169 (54.3%) | 1 | 0.044* | 221 (60.0%) | 210 (56.0%) | 1 | 0.470 |
G/A | 100 (31.1%) | 119 (38.3%) | 1.44 (1.03–2.02) | 125 (34.0%) | 142 (37.9%) | 1.21 (0.89–1.65) | |||
A/A | 16 (5.0%) | 23 (7.4%) | 1.77 (0.90–3.47) | 22 (6.0%) | 23 (6.1%) | 1.10 (0.60–2.04) | |||
Dominant | G/G | 206 (64.0%) | 169 (54.3%) | 1 | 0.015* | 221 (60.0%) | 210 (56.0%) | 1 | 0.240 |
G/A-A/A | 116 (36.0%) | 142 (45.7%) | 1.49 (1.08–2.05) | 147 (40.0%) | 165 (44.0%) | 1.19 (0.89–1.60) | |||
Recessive | G/G-G/A | 306 (95.0%) | 288 (92.6%) | 1 | 0.200 | 346 (94.0%) | 352 (93.9%) | 1 | 0.930 |
A/A | 16 (5.0%) | 23 (7.4%) | 1.54 (0.79–2.99) | 22 (6.0%) | 23 (6.1%) | 1.03 (0.56–1.88) | |||
Log-additive | --- | --- | --- | 1.38 (1.07–1.80) | 0.014* | --- | --- | 1.13 (0.89–1.43) | 0.320 |
Drinking stratification | Drinkers | Non-drinkers | |||||||
Codominant | G/G | 211 (63.0%) | 176 (53.5%) | 1 | 0.042* | 216 (60.9%) | 203 (56.9%) | 1 | 0.600 |
G/A | 101 (30.1%) | 124 (37.7%) | 1.48 (1.06–2.06) | 124 (34.9%) | 137 (38.4%) | 1.16 (0.85–1.59) | |||
A/A | 23 (6.9%) | 29 (8.8%) | 1.53 (0.85–2.75) | 15 (4.2%) | 17 (4.8%) | 1.20 (0.58–2.47) | |||
Dominant | G/G | 211 (63.0%) | 176 (53.5%) | 1 | 0.012* | 216 (60.9%) | 203 (56.9%) | 1 | 0.310 |
G/A-A/A | 124 (37.0%) | 153 (46.5%) | 1.49 (1.09–2.03) | 139 (39.1%) | 154 (43.1%) | 1.17 (0.86–1.58) | |||
Recessive | G/G-G/A | 312 (93.1%) | 300 (91.2%) | 1 | 0.330 | 340 (95.8%) | 340 (95.2%) | 1 | 0.740 |
A/A | 23 (6.9%) | 29 (8.8%) | 1.32 (0.75–2.35) | 15 (4.2%) | 17 (4.8%) | 1.13 (0.55–2.30) | |||
Log-additive | --- | --- | --- | 1.34 (1.05–1.70) | 0.018* | --- | --- | 1.13 (0.88–1.46) | 0.330 |
SNP ID | Model | Genotype | Control | Colon cancer | Rectal cancer | ||||
---|---|---|---|---|---|---|---|---|---|
N | OR (95% CI) | p -value | N | OR (95% CI) | p -value | ||||
rs3740938 | Codominant | G/G | 427 (61.9%) | 179 (55.9%) | 1 | 0.200 | 200 (54.6%) | 1 | 0.064 |
G/A | 225 (32.6%) | 122 (38.1%) | 1.29 (0.97–1.71) | 139 (38.0%) | 1.32 (1.01–1.73) | ||||
A/A | 38 (5.5%) | 19 (5.9%) | 1.19 (0.67–2.13) | 27 (7.4%) | 1.53 (0.90–2.58) | ||||
Dominant | G/G | 427 (61.9%) | 179 (55.9%) | 1 | 0.076 | 200 (54.6%) | 1 | 0.022* | |
G/A-A/A | 263 (38.1%) | 141 (44.1%) | 1.28 (0.98–1.67) | 166 (45.4%) | 1.35 (1.04–1.75) | ||||
Recessive | G/G-G/A | 652 (94.5%) | 301 (94.1%) | 1 | 0.790 | 339 (92.6%) | 1 | 0.230 | |
A/A | 38 (5.5%) | 19 (5.9%) | 1.08 (0.61–1.91) | 27 (7.4%) | 1.37 (0.82–2.29) | ||||
Log-additive | --- | --- | --- | 1.19 (0.96–1.48) | 0.120 | --- | 1.28 (1.04–1.57) | 0.021* | |
rs1940475 | Codominant | C/C | 280 (40.6%) | 127 (39.7%) | 1 | 0.790 | 134 (36.4%) | 1 | 0.240 |
C/T | 313 (45.4%) | 143 (44.7%) | 1.01 (0.76–1.35) | 170 (46.2%) | 1.14 (0.86–1.50) | ||||
T/T | 97 (14.1%) | 50 (15.6%) | 1.15 (0.77–1.71) | 64 (17.4%) | 1.38 (0.95–2.01) | ||||
Dominant | C/C | 280 (40.6%) | 127 (39.7%) | 1 | 0.750 | 134 (36.4%) | 1 | 0.180 | |
C/T-T/T | 410 (59.4%) | 193 (60.3%) | 1.05 (0.80–1.37) | 234 (63.6%) | 1.19 (0.92–1.55) | ||||
Recessive | C/C-C/T | 593 (85.9%) | 270 (84.4%) | 1 | 0.500 | 304 (82.6%) | 1 | 0.160 | |
T/T | 97 (14.1%) | 50 (15.6%) | 1.14 (0.78–1.65) | 64 (17.4%) | 1.29 (0.91–1.82) | ||||
Log-additive | --- | --- | --- | 1.06 (0.87–1.28) | 0.570 | --- | 1.17 (0.97–1.40) | 0.095 | |
rs3765620 | Codominant | A/A | 288 (41.7%) | 128 (40.0%) | 1 | 0.750 | 135 (36.9%) | 1 | 0.240 |
G/A | 309 (44.8%) | 144 (45.0%) | 1.06 (0.79–1.41) | 172 (47.0%) | 1.19 (0.90–1.57) | ||||
G/G | 93 (13.5%) | 48 (15.0%) | 1.17 (0.78–1.76) | 59 (16.1%) | 1.36 (0.92-2.00) | ||||
Dominant | A/A | 288 (41.7%) | 128 (40.0%) | 1 | 0.560 | 135 (36.9%) | 1 | 0.120 | |
G/A-G/G | 402 (58.3%) | 192 (60.0%) | 1.08 (0.83–1.42) | 231 (63.1%) | 1.23 (0.94–1.59) | ||||
Recessive | A/A-G/A | 597 (86.5%) | 272 (85.0%) | 1 | 0.510 | 307 (83.9%) | 1 | 0.240 | |
G/G | 93 (13.5%) | 48 (15.0%) | 1.14 (0.78–1.66) | 59 (16.1%) | 1.24 (0.87–1.77) | ||||
Log-additive | --- | --- | --- | 1.08 (0.89–1.30) | 0.460 | --- | 1.17 (0.97–1.41) | 0.092 |
FPRP analysis
SNP ID | Model | OR (95% CI) | Prior probability | ||||
---|---|---|---|---|---|---|---|
0.25 | 0.1 | 0.01 | 0.001 | 0.0001 | |||
Overall | |||||||
Allele | 1.24 (1.04–1.48) | 0.049 | 0.134 | 0.630 | 0.945 | 0.994 | |
Codominant | 1.31 (1.04–1.64) | 0.053 | 0.143 | 0.647 | 0.949 | 0.995 | |
Dominant | 1.31 (1.06–1.63) | 0.044 | 0.122 | 0.605 | 0.939 | 0.994 | |
Log-additive | 1.24 (1.04–1.47) | 0.038 | 0.106 | 0.567 | 0.930 | 0.992 | |
Females | |||||||
Codominant | 1.55 (1.08–2.22) | 0.052 | 0.141 | 0.644 | 0.948 | 0.995 | |
Dominant | 1.53 (1.09–2.16) | 0.048 | 0.131 | 0.623 | 0.943 | 0.994 | |
Log-additive | 1.37 (1.03–1.81) | 0.075 | 0.195 | 0.727 | 0.964 | 0.996 | |
Age > 60 years | |||||||
Codominant | 1.49 (1.09–2.05) | 0.043 | 0.118 | 0.595 | 0.937 | 0.993 | |
Dominant | 1.44 (1.06–1.94) | 0.048 | 0.131 | 0.624 | 0.944 | 0.994 | |
BMI > 24 kg/m2 | |||||||
Codominant | 1.67 (1.06–2.62) | 0.089 | 0.227 | 0.764 | 0.970 | 0.997 | |
Dominant | 1.74 (1.13–2.69) | 0.049 | 0.135 | 0.631 | 0.945 | 0.994 | |
Log-additive | 1.58 (1.11–2.24) | 0.033 | 0.092 | 0.527 | 0.918 | 0.991 | |
Smokers | |||||||
Codominant | 1.44 (1.03–2.02) | 0.097 | 0.243 | 0.780 | 0.973 | 0.997 | |
Dominant | 1.49 (1.08–2.05) | 0.043 | 0.118 | 0.595 | 0.937 | 0.993 | |
Log-additive | 1.38 (1.07–1.80) | 0.050 | 0.136 | 0.635 | 0.946 | 0.994 | |
Drinkers | |||||||
Codominant | 1.48 (1.06–2.06) | 0.059 | 0.158 | 0.674 | 0.954 | 0.995 | |
Dominant | 1.49 (1.09–2.03) | 0.034 | 0.096 | 0.540 | 0.922 | 0.992 | |
Log-additive | 1.34 (1.05–1.70) | 0.046 | 0.125 | 0.612 | 0.941 | 0.994 | |
Rectal cancer | |||||||
Codominant | 1.32 (1.01–1.73) | 0.117 | 0.285 | 0.814 | 0.978 | 0.998 | |
Dominant | 1.35 (1.04–1.75) | 0.066 | 0.174 | 0.699 | 0.959 | 0.996 | |
Log-additive | 1.28 (1.04–1.57) | 0.051 | 0.138 | 0.638 | 0.947 | 0.994 |
MDR analysis
Model | Training Bal. Acc. | Testing Bal. Acc. | CVC | p |
---|---|---|---|---|
rs3740938 | 0.5336 | 0.5336 | 10/10 | 0.012* |
rs3740938,rs1940475 | 0.5340 | 0.5263 | 9/10 | 0.012* |
rs3740938,rs1940475,rs3765620 | 0.5378 | 0.5270 | 10/10 | 0.005* |