Table 1.
Statistical analysis of association between CRC risk and polymorphisms selected for the study (n = 2144; OR calculations were adjusted according to age and sex).
| Gene Name | Nucleotidic change ** | Proteic change ** | SNP ID ** | Ref *** | Controls | Cases | +/- vs. +/+ | -/- vs. +/+ | +/- and -/- vs. +/+ | ||||||||
| +/+ | +/- | -/- | +/+ | +/- | -/- | OR (95%CI) | p | OR (95% CI) | p | OR (95% CI) | p | ||||||
| Inflammation | ALOX5 | c.760G>A | p.Glu254Lys | rs2228065 | 16 | 1121 | 0 | 0 | 1023 | 0 | 0 | Rare | Rare | Rare | |||
| ALOX12 | c.782G>A | p.Gln261Arg | rs1126667 | 16 | 361 | 549 | 211 | 357 | 498 | 168 | 0.93 (0.76–1.12) | 0.37 | 0.82 (0.63–1.06) | 0.09 | 0.90 (0.75–1.08) | 0.24 | |
| IL6 | c.-239G>C | rs1800795 | 17 | 435 | 504 | 182 | 363 | 489 | 171 | 1.12 (0.92–1.35) | 0.11 | 1.13 (0.87–1.46) | 0.35 | 1.12 (0.94–1.34) | 0.22 | ||
| IL8 | c.-352T>A | rs4073 | 17 | 375 | 516 | 230 | 307 | 511 | 205 | 1.25 (1.03–1.53) | 0.02 | 1.12 (0.88–1.44) | 0.49 | 1.21 (1.01–1.46) | 0.04 | ||
| PLA2G2A | c.-859C>G | rs11573156 | d | 738 | 337 | 46 | 627 | 349 | 47 | 1.20 (1.00–1.45) | 0.05 | 1.16 (0.75–1.78) | 0.39 | 1.20 (1.00–1.43) | 0.05 | ||
| PLA2G2A | c.132C>T | p.Tyr44Tyr | rs4744 | d | 742 | 333 | 46 | 635 | 342 | 46 | 1.17 (0.97–1.42) | 0.05 | 1.13 (0.73–1.73) | 0.47 | 1.17 (0.98–1.40) | 0.09 | |
| PLA2G2A | c.185+88G>A | rs2236772 | d | 1062 | 59 | 0 | 952 | 69 | 2 | 1.30 (0.90–1.88) | 0.14 | Rare | 1.35 (0.94–1.94) | 0.11 | |||
| PLA2G2A | c.435+230C>T | rs11677 | d | 829 | 276 | 16 | 789 | 226 | 8 | 0.82 (0.67–1.01) | 0.07 | 0.50 (0.21–1.19) | 0.13 | 0.80 (0.66–0.98) | 0.03 | ||
| PLD2 | c.1731C>T | p.Thr577Ile | rs1052748 | 18 | 316 | 559 | 246 | 280 | 520 | 223 | 1.05 (0.86–1.29) | 0.63 | 1.00 (0.78–1.27) | 0.85 | 1.04 (0.85–1.26) | 0.82 | |
| PTGS1 | c.22C>T | p.Trp8Arg | rs1236913 | d,32,34 | 976 | 139 | 6 | 879 | 143 | 1 | 1.19 (0.92–1.54) | 0.30 | 0.18 (0.02–1.54) | 0.08 | 1.15 (0.89–1.48) | 0.29 | |
| PTGS1 | c.50C>T | p.Pro17Leu | rs3842787 | d,32,34 | 970 | 147 | 4 | 874 | 142 | 7 | 1.06 (0.82–1.37) | 0.58 | 2.17 (0.62–7.61) | 0.28 | 1.09 (0.85–1.40) | 0.51 | |
| PTGS1 | c.639C>A | p.Gly213Gly | rs5788 | d,32 | 858 | 243 | 20 | 747 | 254 | 22 | 1.24 (1.01–1.53) | 0.03 | 1.26 (0.67–2.36) | 0.45 | 1.24 (1.02–1.52) | 0.03 | |
| PTGS1 | c.123G>A | p.Gln41Gln | rs3842788 | d,32 | 1074 | 47 | 0 | 978 | 45 | 0 | 1.10 (0.72–1.68) | 0.81 | Rare | 1.10 (0.72–1.68) | 0.81 | ||
| PTGS2 | c.-646C>T | rs20420 | d,16 | 1121 | 0 | 0 | 1023 | 0 | 0 | Rare | Rare | Rare | |||||
| PTGS2 | c.306G>C | p.Val102Val | rs5277 | d,31 | 783 | 312 | 26 | 707 | 285 | 31 | 1.00 (0.82–1.21) | 0.90 | 1.25 (0.73–2.16) | 0.30 | 1.02 (0.84–1.23) | 0.85 | |
| PTGS2 | c.1815+427T>C | rs5275 | d,31 | 494 | 499 | 128 | 433 | 476 | 114 | 1.08 (0.90–1.30) | 0.36 | 1.01 (0.76–1.35) | 0.91 | 1.07 (0.90–1.27) | 0.47 | ||
| PTGS2 | c.1815+1912A>G | rs4648298 | d,31 | 1062 | 59 | 0 | 959 | 64 | 0 | 1.31 (0.90–1.89) | 0.32 | Rare | 1.31 (0.90–1.89) | 0.32 | |||
| PPARG | c.36C>G | p.Pro12Ala | rs1801282 | 17 | 896 | 212 | 13 | 822 | 194 | 7 | 1.02 (0.81–1.27) | 0.98 | 0.47 (0.19–1.20) | 0.25 | 0.98 (0.79–1.22) | 0.85 | |
| PPARG | c.1431C>T | p.His477His | rs3856806 | 33 | 875 | 217 | 29 | 803 | 211 | 9 | 1.07 (0.86–1.33) | 0.59 | 0.30 (0.14–0.65) | 0.003 | 0.97 (0.79–1.20) | 0.8 | |
| Xenobiotics | CYP1A2 | c.-163A>C | rs762551 | 19–21 | 554 | 482 | 85 | 520 | 423 | 80 | 0.97 (0.81–1.16) | 0.46 | 1.08 (0.77–1.51) | 0.99 | 0.99 (0.83–1.17) | 0.87 | |
| detoxification | CYP1A2 | c.1548T>C | p.Asn516Asn | rs2470890 | 20,21 | 455 | 525 | 141 | 433 | 467 | 123 | 0.97 (0.81–1.17) | 0.47 | 0.97 (0.73–1.28) | 0.53 | 0.97 (0.81–1.16) | 0.94 |
| CYP2E1 | c.-1293G>C | rs3813867 | 20 | 1032 | 88 | 1 | 954 | 67 | 2 | 0.81 (0.58–1.13) | 0.25 | 2.15 (0.18–25.3) | 0.52 | 0.82 (0.59–1.15) | 0.37 | ||
| CYP2E1 | c.-1053C>T | rs2031920 | 20 | 1030 | 90 | 1 | 950 | 67 | 6 | 0.79 (0.57–1.11) | 0.20 | 5.74 (0.67–49.2) | 0.09 | 0.85 (0.61–1.18) | 0.33 | ||
| CYP1B1 | c.1294C>G | p.Leu432Val | rs1056836 | 19–21 | 370 | 577 | 174 | 322 | 510 | 191 | 0.98 (0.81–1.20) | 0.87 | 1.22 (0.94–1.58) | 0.07 | 1.04 (0.86–1.25) | 0.68 | |
| CYP2C9 | c.430C>T | p.Arg144Cys | rs1799853 | 19–21 | 823 | 281 | 17 | 751 | 251 | 21 | 0.96 (0.79–1.18) | 0.83 | 1.34 (0.69–2.59) | 0.36 | 0.98 (0.81–1.20) | 0.88 | |
| EPHX1 | c.337T>C | p.Tyr113His | rs1051740 | 19–21 | 564 | 469 | 88 | 525 | 409 | 89 | 0.92 (0.77–1.11) | 0.47 | 1.12 (0.81–1.54) | 0.61 | 0.95 (0.80–1.13) | 0.58 | |
| GSTA1 | c.-4605G>A | rs3957356 | 22 | 372 | 549 | 200 | 333 | 517 | 173 | 1.07 (0.88–1.30) | 0.60 | 1.03 (0.79–1.33) | 0.79 | 1.06 (0.88–1.28) | 0.53 | ||
| GSTM1 | null | 19–21 | 161 | 392 | 568 | 174 | 305 | 544 | 0.72 (0.55–0.94) | 0.01 | 0.86 (0.67–1.10) | 0.33 | 0.80 (0.63–1.02) | 0.07 | |||
| GSTM3 | c.468+21delAGG | 19,20 | 788 | 308 | 25 | 679 | 316 | 27 | 1.19 (0.98–1.44) | 0.07 | 1.09 (0.62–1.92) | 0.42 | 1.18 (0.98–1.42) | 0.08 | |||
| GSTP1 | c.313A>G | p.Ile105Val | rs1695 | 19–21 | 511 | 486 | 124 | 465 | 447 | 111 | 1.04 (0.86–1.24) | 0.90 | 0.96 (0.72–1.29) | 0.91 | 1.02 (0.86–1.21) | 0.82 | |
| GSTP1 | c.341C>T | p.Ala114Val | rs1138272 | 19–21 | 966 | 146 | 9 | 882 | 137 | 4 | 1.00 (0.77–1.29) | 0.83 | 0.44 (0.13–1.47) | 0.22 | 0.96 (0.75–1.24) | 0.78 | |
| GSTT1 | null | 19–21 | 433 | 483 | 205 | 411 | 429 | 183 | 0.95 (0.78–1.15) | 0.49 | 0.97 (0.75–1.23) | 0.62 | 0.95 (0.80–1.14) | 0.58 | |||
| NQO1 | c.415C>T | p.Arg139Trp | rs4986998 | 20,21 | 1056 | 65 | 0 | 961 | 62 | 0 | 1.06 (0.74–1.54) | 0.80 | Rare | 1.06 (0.74–1.54) | 0.80 | ||
| NQO1 | c.559C>T | p.Pro187Ser | rs1800566 | 19,21 | 719 | 351 | 51 | 633 | 343 | 47 | 1.09 (0.91–1.32) | 0.26 | 1.08 (0.71–1.64) | 0.83 | 1.09 (0.91–1.31) | 0.34 | |
| SULT1A2 | c.714A>C | p.Asn235Thr | rs1059491 | 21 | 535 | 458 | 128 | 481 | 437 | 105 | 1.09 (0.90–1.31) | 0.52 | 0.92 (0.69–1.23) | 0.53 | 1.05 (0.88–1.25) | 0.58 | |
| UGT1A1 | c.-3279T>G | rs4124874 | 23 | 359 | 546 | 216 | 308 | 515 | 200 | 1.09 (0.90–1.33) | 0.34 | 1.08 (0.84–1.39) | 0.54 | 1.09 (0.90–1.31) | 0.37 | ||
| UGT1A1 | c.-3156G>A | rs10929302 | 23 | 535 | 495 | 91 | 474 | 458 | 91 | 1.03 (0.86–1.24) | 0.65 | 1.11 (0.80–1.53) | 0.45 | 1.04 (0.88–1.24) | 0.63 | ||
| UGT1A6 | c.541A>G | p.Thr181Ala | rs2070959 | 22 | 508 | 504 | 109 | 470 | 443 | 110 | 0.94 (0.78–1.13) | 0.97 | 1.07 (0.80–1.45) | 0.56 | 0.96 (0.81–1.15) | 0.67 | |
| UGT1A6 | c.552A>C | p.Arg184Ser | rs1105879 | 22 | 460 | 529 | 132 | 438 | 454 | 131 | 0.89 (0.74–1.07) | 0.26 | 1.03 (0.77–1.36) | 0.77 | 0.92 (0.77–1.09) | 0.34 | |
| Insulin | GH1 | c.456+90T>A | rs2665802 | 24 | 326 | 561 | 234 | 316 | 527 | 180 | 0.96 (0.79–1.17) | 0.75 | 0.80 (0.62–1.03) | 0.07 | 0.91 (0.76–1.10) | 0.36 | |
| IGF1 | c.-1006CA(19) | 25 | 764 | 152 | 205 | 689 | 159 | 175 | 1.12 (0.87–1.44) | 0.24 | 0.95 (0.75–1.20) | 0.63 | 1.02 (0.85–1.23) | 0.81 | |||
| IGFBP3 | c.-336A>C | rs2854744 | 25 | 287 | 571 | 263 | 259 | 502 | 262 | 0.99 (0.80–1.22) | 0.80 | 1.13 (0.88–1.44) | 0.42 | 1.03 (0.85–1.26) | 0.76 | ||
| IRS1 | c.2911G>A | p.Gly971Arg | rs1801278 | 25 | 956 | 158 | 7 | 865 | 152 | 6 | 1.01 (0.79–1.29) | 0.62 | 0.86 (0.28–2.66) | 0.92 | 1.00 (0.79–1.28) | 0.97 | |
| VDR | c.1024+283G>A | rs1544410 | 25 | 423 | 520 | 178 | 372 | 493 | 158 | 1.11 (0.92–1.35) | 0.43 | 1.06 (0.81–1.37) | 0.94 | 1.10 (0.92–1.31) | 0.31 | ||
| One-carbon | CBS | c.844ins68 | 26,27 | 928 | 185 | 8 | 829 | 185 | 8 | 1.12 (0.89–1.41) | 0.32 | 1.20 (0.44–3.28) | 0.82 | 1.12 (0.90–1.41) | 0.31 | ||
| MTHFD1 | c.1958G>A | p.Arg653Gln | rs2236225 | 28 | 339 | 557 | 225 | 322 | 494 | 207 | 0.91 (0.75–1.12) | 0.49 | 0.99 (0.77–1.27) | 0.80 | 0.94 (0.78–1.13) | 0.48 | |
| MTHFR | c.665C>T | p.Ala222Val | rs1801133 | 26,27 | 457 | 515 | 149 | 435 | 452 | 136 | 0.93 (0.77–1.12) | 0.38 | 0.95 (0.73–1.25) | 0.76 | 0.93 (0.78–1.11) | 0.44 | |
| MTHFR | c.1286A>C | p.Ala429Glu | rs1801131 | 26,27 | 577 | 443 | 101 | 484 | 432 | 107 | 1.20 (1.00–1.45) | 0.04 | 1.26 (0.93–1.70) | 0.12 | 1.21 (1.02–1.44) | 0.03 | |
| MTR | c.2756A>G | p.Asp919Gly | rs1805087 | 26,27 | 742 | 335 | 44 | 706 | 289 | 28 | 0.90 (0.74–1.09) | 0.31 | 0.64 (0.39–1.06) | 0.10 | 0.87 (0.72–1.05) | 0.14 | |
| MTRR | c.66A>G | p.Ile22Met | rs1801394 | 26,27 | 322 | 568 | 231 | 291 | 515 | 217 | 1.01 (0.83–1.24) | 0.97 | 1.01 (0.79–1.30) | 0.75 | 1.01 (0.84–1.23) | 0.89 | |
| TYMS | c.943+447del TTAAAG | 27 | 524 | 482 | 115 | 456 | 456 | 110 | 1.13 (0.94–1.36) | 0.36 | 1.04 (0.77–1.39) | 0.52 | 1.11 (0.94–1.33) | 0.22 | |||
| DNA repair* | OGG1 | c.977C>G | p.Cys326Ser | rs1052133 | 29 | 668 | 402 | 51 | 651 | 321 | 51 | 0.84 (0.69–1.01) | 0.05 | 1.04 (0.69–1.57) | 0.90 | 0.86 (0.72–1.03) | 0.09 |
* SNP OGG1 c.977C>G was chosen to be analyzed together with 6 monoallelic germline mutations of the MUTYH gene – also belonging to the base excision repair system like OGG1 – which were studied previously for their predisposing effect on sporadic CRC (Küry et al., Genet Test; ref [30]).
** Nomenclature referring to the databases dbNSP, SNPPER and SNP500Cancer.
*** Ref: numbers correspond to bibliographical references, and the "d" mark corresponds to SNPs identified by dHPLC screening in 50 patients with CRC and 50 controls from the study population.