Copyright
©The Author(s) 2020.
World J Gastroenterol. Jan 21, 2020; 26(3): 307-323
Published online Jan 21, 2020. doi: 10.3748/wjg.v26.i3.307
Published online Jan 21, 2020. doi: 10.3748/wjg.v26.i3.307
Table 1 Function prediction of nucleotide excision repair polymorphisms in the discovery stage
| SNP | Chromosome | Nearby gene | Allele | Position | nsSNP | Splicing (site) | Splicing (abolish domain) | Splicing (ESE or ESS) | Stop Codon | Polyphen | SNPs3D (svm profile) | SNPs3D (svm structure) | TFBS | miRNA (miRanda) | miRNA (Sanger) | Reg Potential | Conservation |
| rs2029298 | 11 | DDB2 | A/G | Promoter | -- | -- | -- | -- | -- | -- | -- | -- | Y | -- | -- | 0 | 0.001 |
| rs326222 | 11 | DDB2 | C/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0.001 |
| rs3781619 | 11 | DDB2 | A/G | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | NA | 0 |
| rs830083 | 11 | DDB2 | A/C/G/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | NA | 0 |
| rs11615 | 19 | ERCC1 | C/T | Exon | -- | -- | -- | Y | -- | -- | -- | -- | -- | -- | -- | 0.26724 | 0.989 |
| rs2298881 | 19 | ERCC1 | A/C/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | Y | -- | -- | 0.252611 | 0 |
| rs3212955 | 19 | ERCC1 | A/G | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.246701 | 0 |
| rs3212961 | 19 | ERCC1 | A/C/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0 |
| rs3212986 | 19 | ERCC1 | A/C/G/T | Exon | Y | -- | -- | -- | -- | Benign | -- | -- | -- | -- | -- | 0.305187 | 0 |
| rs735482 | 19 | ERCC1 | A/C | Exon | Y | -- | -- | -- | -- | Benign | -- | -- | -- | -- | -- | 0 | 0 |
| rs1052555 | 19 | ERCC2 | C/T | Exon | -- | -- | Y | Y | -- | -- | -- | -- | -- | -- | -- | 0.478925 | 1 |
| rs13181 | 19 | ERCC2 | A/G/T | Exon | Y | -- | Y | Y | -- | Benign | -- | -- | -- | -- | -- | 0.585468 | 0.999 |
| rs238406 | 19 | ERCC2 | G/T | Exon | -- | -- | Y | Y | -- | -- | -- | -- | -- | -- | -- | 0.36557 | 0.996 |
| rs238417 | 19 | ERCC2 | A/C/G | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.037099 | 0 |
| rs50871 | 19 | ERCC2 | G/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0.001 |
| rs50872 | 19 | ERCC2 | A/C/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.137364 | 0.001 |
| rs4150441 | 2 | ERCC3 | A/G | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0 |
| rs4150448 | 2 | ERCC3 | A/G | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0 |
| rs4150506 | 2 | ERCC3 | C/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | NA | 0 |
| rs1799801 | 16 | ERCC4 | C/T | Exon | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.205381 | 0.326 |
| rs2276464 | 16 | ERCC4 | A/C/G | 3'-UTR | -- | -- | -- | -- | -- | -- | -- | -- | -- | Y | Y | 0 | 0 |
| rs254942 | 16 | ERCC4 | A/C/G/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.168034 | 0.005 |
| rs1047768 | 13 | ERCC5 | C/T | Exon | -- | -- | Y | Y | -- | -- | -- | -- | -- | -- | -- | 0.24405 | 0.914 |
| rs2094258 | 13 | ERCC5 | A/G | Promoter | -- | -- | -- | -- | -- | -- | -- | -- | Y | -- | -- | 0 | 0.001 |
| rs2228959 | 13 | ERCC5 | A/C | Exon | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.181402 | 0.509 |
| rs2296147 | 13 | ERCC5 | C/T | Promo-ter | -- | -- | -- | -- | -- | -- | -- | -- | Y | -- | -- | 0.175993 | 0 |
| rs4150291 | 13 | ERCC5 | A/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0 |
| rs4150383 | 13 | ERCC5 | A/G | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0 |
| rs751402 | 13 | ERCC5 | C/T | Promo-ter | -- | -- | Y | Y | -- | -- | -- | -- | Y | -- | -- | 0.25613 | 0 |
| rs873601 | 13 | ERCC5 | A/G | Exon | -- | -- | Y | Y | -- | -- | -- | -- | -- | Y | Y | 0 | 0.005 |
| rs10817938 | 9 | XPA | C/T | Promoter | -- | -- | -- | Y | -- | -- | -- | -- | -- | -- | -- | NA | 0.94 |
| rs2808668 | 9 | XPA | C/G/T | Intron | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0.004 |
| rs3176629 | 9 | XPA | C/T | Promoter | -- | -- | -- | -- | -- | -- | -- | -- | Y | -- | -- | 0 | 0 |
| rs1870134 | 3 | XPC | C/G/T | Exon | Y | -- | -- | Y | -- | -- | -- | -- | -- | -- | -- | 0.272801 | 0 |
| rs2228000 | 3 | XPC | C/T | Exon | Y | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.136701 | 0 |
| rs2228001 | 3 | XPC | A/C | Exon | Y | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0.189938 | 1 |
| rs2470352 | 3 | XPC | A/G/T | Exon | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | -- | 0 | 0 |
| rs2607775 | 3 | XPC | C/G | Exon | -- | -- | -- | Y | -- | -- | -- | -- | Y | -- | -- | 0.282058 | 0 |
Table 2 Association between nucleotide excision repair polymorphisms and colorectal cancer risk in the validation stage1, n (%)
| SNP genotype | NCBI Ref | CRC | CON | P value | OR (95%CI) |
| DDB2 | |||||
| rs2029298 | n = 849 | n = 849 | |||
| GG | 32 (37.2) | 393 (46.3) | 385 (45.3) | 1 (Ref) | |
| GA | 38 (44.2) | 359 (42.3) | 368 (43.3) | 0.650 | 0.95 (0.78-1.17) |
| AA | 16 (18.6) | 97 (11.4) | 96 (11.3) | 0.919 | 0.98 (0.72-1.35) |
| GA + AA vs GG | 0.677 | 0.96 (0.79-1.16) | |||
| AA vs GA + GG | 0.980 | 1.00 (0.74-1.36) | |||
| PHWE | 0.584 | 0.570 | |||
| ERCC1 | |||||
| rs11615 | n = 850 | n = 847 | |||
| CC | 54 (62.8) | 518 (60.9) | 494 (58.3) | 1 (Ref) | |
| CT | 24 (27.9) | 293 (34.5) | 305 (36.0) | 0.355 | 0.91 (0.74-1.11) |
| TT | 8 (9.3) | 39 (4.6) | 48 (5.7) | 0.248 | 0.77 (0.50-1.20) |
| CT + TT vs CC | 0.244 | 0.89 (0.73-1.08) | |||
| TT vs CT + CC | 0.321 | 0.80 (0.52-1.24) | |||
| PHWE | 0.200 | 0.919 | |||
| rs735482 | n = 836 | n = 838 | |||
| CC | 18 (20.9) | 169 (20.2) | 168 (20.0) | 1 (Ref) | |
| CA | 40 (46.5) | 405 (48.4) | 403 (48.1) | 0.966 | 1.00 (0.77-1.28) |
| AA | 28 (32.6) | 262 (31.3) | 267 (31.9) | 0.856 | 0.98 (0.74-1.28) |
| CA + AA vs CC | 0.920 | 0.99 (0.78-1.26) | |||
| AA vs CA + CC | 0.812 | 0.98 (0.79-1.20) | |||
| PHWE | 0.752 | 0.477 | |||
| ERCC2 | |||||
| rs1052555 | n = 852 | n = 851 | |||
| CC | NA | 767 (90.0) | 759 (89.2) | 1 (Ref) | |
| CT | NA | 84 (9.9) | 91 (10.7) | 0.605 | 0.92 (0.67-1.26) |
| TT | NA | 1 (0.1) | 1 (0.1) | 0.970 | 0.95 (0.06-15.21) |
| CT + TT vs CC | 0.602 | 0.92 (0.67-1.26) | |||
| TT vs CT + CC | 0.971 | 0.95 (0.06-15.22) | |||
| PHWE | NA | 0.307 | |||
| rs50871 | n = 838 | n = 845 | |||
| TT | 40 (46.5) | 429 (51.2) | 451 (53.4) | 1 (Ref) | |
| TG | 36 (41.9) | 337 (40.2) | 358 (42.4) | 0.922 | 0.99 (0.81-1.21) |
| GG | 10 (11.6) | 72 (8.6) | 36 (4.3) | 0.001 | 2.09 (1.37-3.19) |
| TG + GG vs TT | 0.374 | 1.09 (0.90-1.32) | |||
| GG vs TG + TT | < 0.001 | 2.08 (1.38-3.15) | |||
| PHWE | 1.000 | 0.001 | |||
| ERCC5 | |||||
| rs1047768 | n = 839 | n = 845 | |||
| CC | 8 (9.3) | 75 (8.9) | 71 (8.4) | 1 (Ref) | |
| CT | 30 (34.9) | 348 (41.5) | 351 (41.5) | 0.735 | 0.94 (0.66-1.35) |
| TT | 48 (55.8) | 416 (49.6) | 423 (50.1) | 0.708 | 0.94 (0.66-1.33) |
| CT + TT vs CC | 0.717 | 0.94 (0.67-1.32) | |||
| TT vs CT + CC | 0.822 | 0.98 (0.81-1.19) | |||
| PHWE | 0.480 | 0.880 | |||
| rs2094258 | n = 843 | n = 841 | |||
| GG | 38 (44.2) | 307 (36.4) | 326 (38.8) | 1 (Ref) | |
| GA | 42 (48.8) | 409 (48.5) | 392 (46.6) | 0.389 | 1.10 (0.89-1.35) |
| AA | 6 (7.0) | 127 (15.1) | 123 (14.6) | 0.615 | 1.08 (0.80-1.45) |
| GA + AA vs GG | 0.370 | 1.10 (0.90-1.33) | |||
| AA vs GA + GG | 0.837 | 1.03 (0.79-1.35) | |||
| PHWE | 0.403 | 0.770 | |||
| rs2228959 | n = 841 | n = 851 | |||
| CC | 74 (86.0) | 754 (89.7) | 782 (91.9) | 1 (Ref) | |
| CA | 12 (14.0) | 83 (9.9) | 62 (7.3) | 0.051 | 1.41 (1.00-1.99) |
| AA | 0 (0.0) | 4 (0.5) | 7 (0.8) | 0.408 | 0.59 (0.17-2.04) |
| CA + AA vs CC | 0.095 | 1.33 (0.95-1.85) | |||
| AA vs CA + CC | 0.383 | 0.58 (0.17-1.98) | |||
| PHWE | 1.000 | < 0.001 | |||
| rs2296147 | n = 844 | n = 847 | |||
| TT | 52 (60.5) | 508 (60.2) | 517 (61.0) | 1 (Ref) | |
| TC | 32 (37.2) | 294 (34.8) | 289 (34.1) | 0.684 | 1.04 (0.85-1.28) |
| CC | 2 (2.3) | 42 (5.0) | 41 (4.8) | 0.904 | 1.03 (0.66-1.61) |
| TC + CC vs TT | 0.679 | 1.04 (0.86-1.27) | |||
| CC vs TC + TT | 0.952 | 1.01 (0.65-1.58) | |||
| PHWE | 0.439 | 0.940 | |||
| rs873601 | n = 842 | n = 837 | |||
| GG | 16 (18.6) | 230 (27.3) | 223 (26.6) | 1 (Ref) | |
| GA | 48 (55.8) | 435 (51.7) | 413 (49.3) | 0.807 | 1.03 (0.82-1.29) |
| AA | 22 (25.6) | 177 (21.0) | 201 (24.0) | 0.310 | 0.87 (0.66-1.14) |
| GA + AA vs GG | 0.849 | 0.98 (0.79-1.22) | |||
| AA vs GA + GG | 0.155 | 0.85 (0.67-1.07) | |||
| PHWE | 0.439 | 0.719 | |||
| XPA | |||||
| rs10817938 | n = 823 | n = 822 | |||
| TT | 58 (67.4) | 511 (62.1) | 547 (66.5) | 1(Ref) | |
| TC | 24 (27.9) | 259 (31.5) | 241 (29.3) | 0.231 | 1.14 (0.92-1.41) |
| CC | 4 (4.7) | 53 (6.4) | 34 (4.1) | 0.021 | 1.70 (1.08-2.66) |
| TC + CC vs TT | 0.071 | 1.21 (0.98-1.48) | |||
| CC vs TC + TT | 0.033 | 1.62 (1.04-2.52) | |||
| PHWE | 0.655 | 0.257 | |||
| rs3176629 | n = 847 | n = 852 | |||
| CC | 68 (79.1) | 689 (81.3) | 706 (82.9) | 1 (Ref) | |
| CT | 18 (20.9) | 151 (17.8) | 133 (15.6) | 0.240 | 1.17 (0.90-1.51) |
| TT | 0 (0.0) | 7 (0.8) | 13 (1.5) | 0.225 | 0.56 (0.22-1.42) |
| CT + TT vs CC | 0.399 | 1.11 (0.87-1.43) | |||
| TT vs CT + CC | 0.205 | 0.55 (0.22-1.39) | |||
| PHWE | 0.752 | 0.024 | |||
| XPC | |||||
| rs2607775 | n = 840 | n = 850 | |||
| CC | 76 (84.5) | 755 (89.9) | 792 (93.2) | 1(Ref) | |
| CG | 12 (13.3) | 80 (9.5) | 56 (6.6) | 0.027 | 1.49 (1.05-2.13) |
| GG | 2 (2.2) | 5 (0.6) | 2 (0.2) | 0.219 | 2.81 (0.54-14.56) |
| CG + GG vs CC | 0.016 | 1.54 (1.09-2.18) | |||
| GG vs CG + CC | 0.238 | 2.69 (0.52-13.95) | |||
| PHWE | 0.251 | 0.343 |
Table 3 Cumulative effect of nucleotide excision repair polymorphisms associated with colorectal cancer risk1, n (%)
| Number of SNP risk genotypes | CRC | CON | P value | OR (95%CI) |
| n = 841 | n = 847 | |||
| 0 | 706 (83.9) | 755 (89.1) | 1 (Ref) | |
| 1 | 131 (15.6) | 92 (10.9) | 0.004 | 1.53 (1.15-2.04) |
| 2 | 4 (0.5) | 0 (0.0) | NA | NA |
| Ptrend = 0.001 | ||||
Table 4 Effect of interaction between nucleotide excision repair polymorphisms and environmental factors on colorectal cancer risk1
| SNP genotype | Smoking | Drinking | Helicobacter pylori infection | |||
| No | Yes | No | Yes | Negative | Positive | |
| DDB2 | ||||||
| rs2029298 | n = 981 | n = 468 | n = 1190 | n = 257 | n = 810 | n = 443 |
| GA + AA | ||||||
| Case/Control | 312/220 | 142/104 | 367/274 | 87/49 | 164/286 | 189/44 |
| OR (95%CI) | 1 (Ref) | 0.96 (0.71-1.31) | 1 (Ref) | 1.33 (0.90-1.95) | 1 (Ref) | 7.49 (5.12-10.96) |
| GG | ||||||
| Case/Control | 267/182 | 124/98 | 330/219 | 61/60 | 140/220 | 158/52 |
| OR (95%CI) | 1.03 (0.80-1.34) | 0.89 (0.65-1.22) | 1.13 (0.89-1.42) | 0.76 (0.51-1.12) | 1.11 (0.83-1.48) | 5.30 (3.67-7.65) |
| Pinteraction = 0.618 | Pinteraction = 0.019 OR (95%CI) = 0.52 (0.30-0.90) | Pinteraction = 0.095 | ||||
| ERCC1 | ||||||
| rs11615 | n = 982 | n = 467 | n = 1190 | n = 257 | n = 812 | n = 444 |
| CT + TT | ||||||
| Case/Control | 231/160 | 101/88 | 278/205 | 54/40 | 110/210 | 146/42 |
| OR (95%CI) | 1 (Ref) | 0.80 (0.56-1.13) | 1 (Ref) | 1.00 (0.64-1.56) | 1 (Ref) | 6.64 (4.39-10.04) |
| CC | ||||||
| Case/Control | 349/242 | 165/113 | 421/286 | 93/70 | 194/298 | 203/53 |
| OR (95%CI) | 1.00 (0.77-1.30) | 1.01 (0.74-1.38) | 1.09 (0.86-1.37) | 0.98 (0.68-1.40) | 1.24 (0.93-1.67) | 7.31 (5.00-10.70) |
| Pinteraction = 0.309 | Pinteraction = 0.749 | Pinteraction = 0.642 | ||||
| rs735482 | n = 968 | n = 461 | n = 1171 | n = 256 | n = 803 | n = 434 |
| AA | ||||||
| Case/Control | 175/124 | 87/64 | 213/148 | 49/40 | 89/161 | 115/24 |
| OR (95%CI) | 1 (Ref) | 0.96 (0.65-1.43) | 1 (Ref) | 0.85 (0.53-1.36) | 1 (Ref) | 8.67 (5.20-14.44) |
| CA + CC | ||||||
| Case/Control | 396/273 | 174/136 | 471/339 | 99/68 | 212/341 | 224/71 |
| OR (95%CI) | 1.03 (0.78-1.36) | 0.91 (0.66-1.25) | 0.97 (0.75-1.24) | 1.01 (0.70-1.47) | 1.13 (0.82-1.53) | 5.71 (3.94-8.28) |
| Pinteraction = 0.638 | Pinteraction = 0.446 | Pinteraction = 0.082 | ||||
| ERCC2 | ||||||
| rs1052555 | n = 986 | n = 468 | n = 1193 | n = 259 | n = 811 | n = 447 |
| CT + TT | ||||||
| Case/Control | 55/39 | 30/27 | 68/56 | 17/10 | 27/54 | 39/11 |
| OR (95%CI) | 1 (Ref) | 0.79 (0.41-1.53) | 1 (Ref) | 1.40 (0.59-3.30) | 1 (Ref) | 7.09 (3.15-15.99) |
| CC | ||||||
| Case/Control | 527/365 | 236/175 | 632/437 | 131/101 | 277/453 | 312/85 |
| OR (95%CI) | 1.02 (0.67-1.58) | 0.96 (0.61-1.51) | 1.19 (0.82-1.73) | 1.07 (0.69-1.66) | 1.22 (0.75-1.99) | 7.34 (4.36-12.35) |
| Pinteraction = 0.624 | Pinteraction = 0.319 | Pinteraction = 0.712 | ||||
| ERCC5 | ||||||
| rs1047768 | n = 973 | n = 464 | n = 1177 | n = 258 | n = 808 | n = 437 |
| CT + TT | ||||||
| Case/Control | 524/368 | 236/190 | 622/452 | 138/103 | 272/460 | 317/88 |
| OR (95%CI) | 1 (Ref) | 0.87 (0.69-1.10) | 1 (Ref) | 0.97 (0.73-1.29) | 1 (Ref) | 6.09 (4.61-8.06) |
| CC | ||||||
| Case/Control | 49/32 | 26/12 | 66/37 | 9/8 | 29/47 | 26/6 |
| OR (95%CI) | 1.08 (0.68-1.71) | 1.52 (0.76-3.06) | 1.30 (0.85-1.97) | 0.82 (0.31-2.14) | 1.04 (0.64-1.70) | 7.33 (2.98-18.03) |
| Pinteraction = 0.241 | Pinteraction = 0.491 | Pinteraction = 0.843 | ||||
| rs2094258 | n = 973 | n = 464 | n = 1180 | n = 255 | n = 805 | n = 443 |
| GG | ||||||
| Case/Control | 209/150 | 97/70 | 251/180 | 55/40 | 119/203 | 116/38 |
| OR (95%CI) | 1 (Ref) | 1.00 (0.69-1.44) | 1 (Ref) | 0.99 (0.63-1.55) | 1 (Ref) | 5.21 (3.39-8.01) |
| GA + AA | ||||||
| Case/Control | 364/250 | 169/128 | 442/307 | 91/69 | 181/302 | 233/56 |
| OR (95%CI) | 1.05 (0.80-1.36) | 0.95 (0.69-1.29) | 1.03 (0.81-1.31) | 0.95 (0.66-1.37) | 1.02 (0.76-1.37) | 7.10 (4.91-10.27) |
| Pinteraction = 0.587 | Pinteraction = 0.685 | Pinteraction = 0.314 | ||||
| rs2296147 | n = 979 | n = 466 | n = 1185 | n = 258 | n = 807 | n = 440 |
| TT | ||||||
| Case/Control | 356/251 | 151/126 | 426/301 | 81/75 | 184/298 | 207/59 |
| OR (95%CI) | 1 (Ref) | 0.85 (0.64-1.13) | 1 (Ref) | 0.76 (0.54-1.08) | 1 (Ref) | 5.68 (4.03-8.01) |
| TC+CC | ||||||
| Case/Control | 221/151 | 112/77 | 268/190 | 65/37 | 118/207 | 138/36 |
| OR (95%CI) | 1.03 (0.79-1.34) | 1.03 (0.74-1.43) | 1.00 (0.79-1.26) | 1.24 (0.81-1.91) | 0.92 (0.69-1.24) | 6.21 (4.12-9.36) |
| Pinteraction = 0.506 | Pinteraction = 0.089 | Pinteraction = 0.562 | ||||
| rs873601 | n = 974 | n = 462 | n = 1179 | n = 255 | n = 798 | n = 439 |
| AA | ||||||
| Case/Control | 130/94 | 47/51 | 148/116 | 29/28 | 69/126 | 75/25 |
| OR (95%CI) | 1 (Ref) | 0.67 (0.41-1.07) | 1 (Ref) | 0.81 (0.46-1.44) | 1 (Ref) | 5.48 (3.19-9.40) |
| GA + GG | ||||||
| Case/Control | 446/304 | 215/149 | 543/372 | 118/80 | 234/369 | 269/70 |
| OR (95%CI) | 1.06 (0.78-1.44) | 1.04 (0.74-1.46) | 1.14 (0.87-1.51) | 1.16 (0.80-1.68) | 1.16 (0.83-1.62) | 7.02 (4.73-10.41) |
| Pinteraction = 0.202 | Pinteraction = 0.550 | Pinteraction = 0.764 | ||||
| XPA | ||||||
| rs10817938 | n = 952 | n = 453 | n = 1152 | n = 252 | n = 785 | n = 429 |
| TC + TT | ||||||
| Case/Control | 527/380 | 239/183 | 631/459 | 135/103 | 281/470 | 311/88 |
| OR (95%CI) | 1 (Ref) | 0.94 (0.75-1.19) | 1 (Ref) | 0.95 (0.72-1.27) | 1 (Ref) | 5.91 (4.47-7.81) |
| CC | ||||||
| Case/Control | 33/12 | 20/11 | 45/17 | 8/6 | 14/20 | 25/5 |
| OR (95%CI) | 1.98 (1.01-3.89) | 1.31 (0.62-2.77) | 1.93 (1.09-3.41) | 0.97 (0.33-2.81) | 1.17 (0.58-2.36) | 8.36 (3.17-22.09) |
| Pinteraction = 0.516 | Pinteraction = 0.299 | Pinteraction = 0.738 | ||||
| XPC | ||||||
| rs2607775 | n = 979 | n = 463 | n = 1184 | n = 256 | n = 809 | n = 439 |
| CC | ||||||
| Case/Control | 513/369 | 238/195 | 617/458 | 134/103 | 273/475 | 314/88 |
| OR (95%CI) | 1 (Ref) | 0.88 (0.70-1.11) | 1 (Ref) | 0.97 (0.73-1.28) | 1 (Ref) | 6.21 (4.70-8.21) |
| CG + GG | ||||||
| Case/Control | 61/36 | 24/6 | 73/36 | 12/7 | 28/33 | 30/7 |
| OR (95%CI) | 1.22 (0.79-1.88) | 2.88 (1.16-7.11) | 1.51 (0.99-2.28) | 1.27 (0.50-3.26) | 1.48 (0.87-2.50) | 7.46 (3.23-17.21) |
| Pinteraction=0.066 | Pinteraction=0.728 | Pinteraction=0.766 | ||||
Table 5 Association between host factors and the overall survival of colorectal cancer patients
| Factor | CRC patients | Death | MST (M) | P value |
| Total | n = 565 | n = 95 | ||
| Gender | 0.862 | |||
| Male | 384 | 63 | 46.61 | |
| Female | 181 | 32 | 47.11 | |
| Age (yr) | 0.127 | |||
| ≤ 60 | 322 | 46 | 47.91 | |
| > 60 | 243 | 49 | 44.71 | |
| Smoking | 0.111 | |||
| Ever Smoker | 180 | 23 | 48.71 | |
| Never Smoker | 383 | 72 | 45.91 | |
| Drinking | 0.157 | |||
| Drinker | 107 | 14 | 49.31 | |
| Non-drinker | 456 | 81 | 46.11 | |
| TNM stage | < 0.001 | |||
| I + II | 336 | 23 | 52.11 | |
| III + IV | 223 | 69 | 48 | |
| Macroscopic type | < 0.001 | |||
| Protrude type | 104 | 5 | 53.41 | |
| Ulcerative/Invasive type | 458 | 90 | 45.21 | |
| Histological type | < 0.001 | |||
| High/Middle differentiation | 367 | 40 | 50.21 | |
| Low differentiation | 196 | 55 | 39.31 | |
| Depth of invasion | < 0.001 | |||
| T1 + T2 | 114 | 6 | 53.41 | |
| T3 + T4 | 450 | 89 | 44.91 | |
| Growth mode | < 0.001 | |||
| Nest | 236 | 18 | 52.11 | |
| Invasion | 326 | 77 | 42.61 | |
| Lymphatic metastasis | < 0.001 | |||
| Positive | 217 | 68 | 47 | |
| Negative | 342 | 24 | 52.01 |
Table 6 Association between nucleotide excision repair polymorphisms and colorectal cancer prognosis
| SNP genotype | CRC patients | Death | MST (M) | Univariate | Multivariate | ||
| P value | HR (95%CI) | P value | HR (95%CI) | ||||
| DDB2 | |||||||
| rs2029298 | n = 560 | n = 94 | |||||
| GG | 262 | 50 | 44.41 | 1(Ref) | 1 (Ref) | ||
| GA | 230 | 35 | 47.41 | 0.368 | 0.82 (0.53-1.26) | 0.393 | 0.82 (0.53-1.29) |
| AA | 68 | 9 | 48.61 | 0.265 | 0.67 (0.33-1.36) | 0.467 | 0.77 (0.37-1.57) |
| GA + AA vs GG | 0.235 | 0.78 (0.52-1.17) | 0.307 | 0.81 (0.53-1.22) | |||
| AA vs GA + GG | 0.370 | 0.73 (0.37-1.45) | 0.581 | 0.82 (0.41-1.65) | |||
| ERCC1 | |||||||
| rs11615 | n = 561 | n = 95 | |||||
| CC | 345 | 62 | 46.41 | 1 (Ref) | 1 (Ref) | ||
| CT | 188 | 29 | 47.21 | 0.647 | 0.90 (0.58-1.40) | 0.947 | 1.02 (0.65-1.59) |
| TT | 28 | 4 | 45.81 | 0.955 | 0.97 (0.35-2.67) | 0.975 | 0.98 (0.35-2.76) |
| CT + TT vs CC | 0.662 | 0.91 (0.60-1.39) | 0.974 | 0.99 (0.65-1.53) | |||
| TT vs CT + CC | 0.999 | 1.00 (0.37-2.73) | 0.911 | 0.94 (0.34-2.60) | |||
| rs735482 | n = 552 | n = 91 | |||||
| CC | 123 | 23 | 46.81 | 1 (Ref) | 1 (Ref) | ||
| CA | 258 | 38 | 47.31 | 0.982 | 0.99 (0.59-1.67) | 0.582 | 1.16 (0.69-1.96) |
| AA | 171 | 30 | 45.51 | 0.603 | 1.16 (0.67-1.99) | 0.774 | 0.92 (0.53-1.61) |
| CA + AA vs CC | 0.829 | 1.05 (0.66-1.69) | 0.923 | 1.02 (0.64-1.65) | |||
| AA vs CA + CC | 0.517 | 1.16 (0.75-1.79) | 0.521 | 0.86 (0.55-1.35) | |||
| ERCC2 | |||||||
| rs1052555 | n = 563 | n = 95 | |||||
| CC | 506 | 86 | 46.61 | 1 (Ref) | 1 (Ref) | ||
| CT | 56 | 8 | 48.31 | 0.377 | 0.72 (0.35-1.49) | 0.998 | 1.00 (0.48-2.09) |
| TT | 1 | 1 | 2 | < 0.001 | 49.73 (6.37-388.47) | 0.010 | 14.99 (1.90-118.10) |
| CT + TT vs CC | 0.551 | 0.81 (0.41-1.61) | 0.744 | 1.12 (0.56-2.26) | |||
| TT vs CT + CC | < 0.001 | 55.22 (7.07-431.35) | 0.009 | 15.89 (2.02-125.16) | |||
| rs50871 | n = 551 | n = 92 | |||||
| TT | 294 | 43 | 47.01 | 1 (Ref) | 1 (Ref) | ||
| TG | 210 | 40 | 45.71 | 0.256 | 1.28 (0.83-1.98) | 0.446 | 1.19 (0.77-1.84) |
| GG | 47 | 9 | 45.81 | 0.541 | 1.25 (0.61-2.57) | 0.576 | 0.80 (0.37-1.74) |
| TG + GG vs TT | 0.239 | 1.28 (0.85-1.93) | 0.646 | 1.10 (0.73-1.68) | |||
| GG vs TG + TT | 0.749 | 1.12 (0.56-2.23) | 0.354 | 0.71 (0.34-1.47) | |||
| ERCC5 | |||||||
| rs1047768 | n = 553 | n = 92 | |||||
| CC | 55 | 9 | 46.71 | 1 (Ref) | 1 (Ref) | ||
| CT | 233 | 44 | 46.51 | 0.785 | 1.11 (0.54-2.26) | 0.945 | 0.97 (0.45-2.09) |
| TT | 265 | 39 | 47.01 | 0.933 | 1.03 (0.50-2.13) | 0.542 | 0.78 (0.36-1.72) |
| CT + TT vs CC | 0.851 | 1.07 (0.54-2.13) | 0.768 | 0.90 (0.43-1.87) | |||
| TT vs CT + CC | 0.799 | 0.95 (0.63-1.43) | 0.387 | 0.83 (0.54-1.27) | |||
| rs2094258 | n = 555 | n = 93 | |||||
| GG | 207 | 38 | 46.61 | 1 (Ref) | 1 (Ref) | ||
| GA | 269 | 42 | 47.01 | 0.721 | 0.92 (0.60-1.43) | 0.400 | 0.82 (0.53-1.29) |
| AA | 79 | 13 | 44.31 | 0.973 | 0.99 (0.53-1.86) | 0.588 | 0.84 (0.44-1.59) |
| GA + AA vs GG | 0.773 | 0.94 (0.62-1.42) | 0.424 | 0.84 (0.55-1.29) | |||
| AA vs GA + GG | 0.869 | 1.05 (0.59-1.89) | 0.916 | 1.03 (0.57-1.87) | |||
| rs2228959 | n = 558 | n = 93 | |||||
| CC | 501 | 82 | 47.11 | 1 (Ref) | 1 (Ref) | ||
| CA | 53 | 9 | 45.41 | 0.768 | 1.11 (0.56-2.21) | 0.811 | 0.92 (0.46-1.85) |
| AA | 4 | 2 | 13.81 | 0.006 | 7.18 (1.75-29.50) | 0.046 | 4.32 (1.03-18.17) |
| CA + AA vs CC | 0.402 | 1.31 (0.70-2.46) | 0.847 | 1.07 (0.56-2.02) | |||
| AA vs CA + CC | 0.006 | 7.16 (1.75-29.32) | 0.049 | 4.20 (1.00-17.60) | |||
| rs2296147 | n = 556 | n = 92 | |||||
| TT | 318 | 46 | 47.41 | 1 (Ref) | 1 (Ref) | ||
| TC | 207 | 42 | 45.41 | 0.384 | 1.21 (0.79-1.83) | 0.194 | 1.32 (0.87-2.02) |
| CC | 31 | 4 | 48.11 | 0.691 | 0.81 (0.29-2.26) | 0.658 | 1.32 (0.38-4.57) |
| TC + CC vs TT | 0.484 | 1.16 (0.77-1.74) | 0.184 | 1.33 (0.87-2.02) | |||
| CC vs TC + TT | 0.573 | 0.75 (0.28-2.04) | 0.978 | 1.02 (0.31-3.32) | |||
| rs873601 | n = 558 | n = 95 | |||||
| GG | 140 | 21 | 47.51 | 1 (Ref) | 1 (Ref) | ||
| GA | 301 | 49 | 46.91 | 0.745 | 1.09 (0.65-1.82) | 0.923 | 0.98 (0.58-1.64) |
| AA | 117 | 25 | 44.51 | 0.293 | 1.37 (0.76-2.44) | 0.713 | 1.12 (0.62-2.03) |
| GA + AA vs GG | 0.526 | 1.17 (0.72-1.90) | 0.951 | 1.02 (0.62-1.66) | |||
| AA vs GA + GG | 0.275 | 1.29 (0.82-2.04) | 0.473 | 1.19 (0.74-1.90) | |||
| XPA | |||||||
| rs10817938 | n = 545 | n = 93 | |||||
| TT | 351 | 61 | 46.61 | 1 (Ref) | 1 (Ref) | ||
| TC | 163 | 29 | 46.21 | 0.815 | 1.05 (0.68-1.64) | 0.472 | 1.18 (0.75-1.88) |
| CC | 31 | 3 | 49.51 | 0.429 | 0.63 (0.20-2.00) | 0.903 | 0.93 (0.29-3.02) |
| TC + CC vs TT | 0.968 | 0.99 (0.65-1.52) | 0.489 | 1.17 (0.75-1.83) | |||
| CC vs TC+TT | 0.414 | 0.62 (0.20-1.96) | 0.863 | 0.90 (0.28-2.89) | |||
| rs3176629 | n = 558 | n = 94 | |||||
| CC | 450 | 74 | 47.01 | 1 (Ref) | 1 (Ref) | ||
| CT | 103 | 19 | 44.81 | 0.470 | 1.20 (0.73-1.99) | 0.420 | 0.81 (0.48-1.36) |
| TT | 5 | 1 | 49.31 | 0.824 | 0.80 (0.11-5.76) | 0.660 | 0.64 (0.09-4.64) |
| CT + TT vs CC | 0.521 | 1.18 (0.72-1.93) | 0.375 | 0.79 (0.47-1.33) | |||
| TT vs CT + CC | 0.787 | 0.76 (0.11-5.47) | 0.690 | 0.67 (0.09-4.82) | |||
| XPC | |||||||
| rs2607775 | n = 556 | n = 92 | |||||
| CC | 494 | 84 | 46.81 | 1 (Ref) | 1 (Ref) | ||
| CG | 57 | 8 | 46.31 | 0.739 | 0.88 (0.43-1.83) | 0.842 | 0.93 (0.44-1.94) |
| GG | 5 | 0 | NA | 0.525 | NA | 0.969 | NA |
| CG + GG vs CC | 0.555 | 0.80 (0.39-1.66) | 0.604 | 0.82 (0.40-1.72) | |||
| GG vs CG + CC | 0.528 | NA | 0.970 | NA | |||
- Citation: Li YK, Xu Q, Sun LP, Gong YH, Jing JJ, Xing CZ, Yuan Y. Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer. World J Gastroenterol 2020; 26(3): 307-323
- URL: https://www.wjgnet.com/1007-9327/full/v26/i3/307.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i3.307