supplementary table 1

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Fam ily history Youngeronsetpatients (firstdegree relative) ( 60 years old) Screening stage 1583 35.50% 62.80% Firstreplication 3099 3.62% 21.17% Second replicatio 1485 8.28% 21.62% N um berofcases Supplementary Table 1

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Supplementary Table 1. Supplementary Table 2 The results of screening stage analysis of colorectal cancer . - PowerPoint PPT Presentation

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Page 1: Supplementary Table  1

Family history Younger onset patients (first degree relative) ( 60 years old)

Screening stage 1583 35.50% 62.80%First replication 3099 3.62% 21.17%Second replication 1485 8.28% 21.62%

Number of cases

Supplementary Table 1

Page 2: Supplementary Table  1

Allele Chromosome p Value(1/2) (position) 11 12 22 SUM MAF 11 12 22 SUM MAF (HWE)||

rs11003722 (A/G) No gene 10q (55064621) 204 720 659 1583 0.36 190 760 948 1898 0.30 0.040 1.29 (1.17~1.43) 1.04E-06rs7988900 (T/C) No gene 13q (97276536) 866 612 105 1583 0.26 888 831 176 1895 0.31 0.356 0.78 (0.69~0.86) 1.29E-06rs2600814 (T/C) No gene 14q (46054248) 3 191 1389 1583 0.06 14 325 1559 1898 0.09 0.511 0.65 (0.54~0.78) 1.72E-06rs10825073 (T/C) No gene 10q (55041607) 156 667 760 1583 0.31 151 679 1068 1898 0.26 0.004 1.28 (1.16~1.43) 4.39E-06rs6481026 (A/G) No gene 10q (55041794) 156 666 760 1582 0.31 151 679 1068 1898 0.26 0.004 1.28 (1.16~1.43) 4.65E-06rs4841926 (T/C) COL5A1 9q (136741106) 609 728 246 1583 0.39 576 979 343 1898 0.44 0.039 0.80 (0.73~0.88) 6.28E-06rs17589429 (T/C) CELSR1 22q (45294944) 892 592 99 1583 0.25 1194 630 73 1897 0.20 0.370 1.30 (1.15~1.45) 7.07E-06rs12412826 (A/G) APBB1IP 10p (26818612) 19 341 1223 1583 0.12 10 312 1576 1898 0.09 0.194 1.42 (1.21~1.66) 7.59E-06rs11745068 (T/G) No gene 5q (134503393) 475 757 351 1583 0.46 686 881 331 1898 0.41 0.098 1.25 (1.14~1.37) 7.83E-06rs4823839 (T/C) CELSR1 22q (45292438) 72 571 940 1583 0.23 73 547 1278 1898 0.18 0.134 1.31 (1.16~1.47) 7.97E-06rs6428571 (T/C) No gene 1p2 (90373522) 8 220 1355 1583 0.07 28 346 1524 1898 0.11 0.104 0.68 (0.57~0.80) 8.04E-06rs7095328 (T/C) No gene 10q (55055968) 139 664 780 1583 0.30 143 659 1095 1897 0.25 0.002 1.28 (1.15~1.42) 8.80E-06rs566750 (A/G) No gene 5q (134513184) 629 738 216 1583 0.37 877 831 190 1898 0.32 0.738 1.25 (1.14~1.39) 9.47E-06rs7906396 (T/C) No gene 10q (55061615) 545 755 283 1583 0.42 780 852 266 1898 0.36 0.175 1.25 (1.14~1.37) 9.62E-06rs17685664 (T/C) FER1L5 2q (96679297) 36 347 1199 1582 0.13 23 326 1549 1898 0.10 0.215 1.40 (1.21~1.63) 9.93E-06rs6983267 (T/G) No gene 8q (128482487) 593 757 233 1583 0.39 826 869 203 1898 0.34 0.252 1.25 (1.12~1.37) 1.08E-05rs3128591 (A/G) COL5A1 9q (136741940) 611 724 248 1583 0.39 580 977 341 1898 0.44 0.045 0.81 (0.74~0.89) 1.20E-05rs7078645 (A/G) No gene 10q (55065324) 549 752 281 1582 0.42 784 849 265 1898 0.36 0.150 1.25 (1.14~1.37) 1.24E-05rs1559050 (A/G) No gene 5q (134497929) 550 752 281 1583 0.42 771 873 253 1897 0.36 0.813 1.25 (1.12~1.37) 1.28E-05rs2314109 (T/C) No gene 2q (96607259) 36 345 1202 1583 0.13 23 325 1548 1896 0.10 0.207 1.40 (1.21~1.62) 1.35E-05rs7097226 (A/C) No gene 10q (55065386) 281 752 550 1583 0.42 265 849 784 1898 0.36 0.150 1.24 (1.13~1.37) 1.36E-05rs2579502 (T/C) No gene 2q (96562527) 36 345 1202 1583 0.13 23 326 1549 1898 0.10 0.215 1.40 (1.20~1.62) 1.48E-05rs11003740 (A/C) No gene 10q (55088093) 537 759 287 1583 0.42 755 882 261 1898 0.37 0.894 1.24 (1.12~1.37) 1.51E-05rs3909811 (T/G) No gene 5q (134516248) 604 733 246 1583 0.39 837 844 217 1898 0.34 0.848 1.24 (1.12~1.37) 1.59E-05rs2874568 (T/C) No gene 4q (165584384) 1093 452 38 1583 0.17 1438 426 34 1898 0.13 0.707 1.34 (1.18~1.54) 1.59E-05rs10238157 (A/G) No gene 7q (125324655) 694 690 199 1583 0.34 956 766 176 1898 0.29 0.209 1.25 (1.14~1.39) 1.60E-05rs2174919 (A/G) No gene 17q (72758874) 769 648 166 1583 0.31 780 873 245 1898 0.36 0.976 0.80 (0.72~0.88) 1.65E-05rs6753667 (A/G) No gene 2q (96524109) 1161 378 44 1583 0.15 1502 367 29 1898 0.11 0.229 1.37 (1.19~1.59) 1.75E-05rs3935335 (A/G) COL5A1 9q (136735987) 603 731 249 1583 0.39 575 971 344 1890 0.44 0.061 0.81 (0.74~0.89) 1.80E-05rs7042608 (A/G) No gene 9q (125991105) 6 196 1381 1583 0.07 20 317 1561 1898 0.09 0.387 0.68 (0.57~0.81) 1.80E-05rs12434073 (A/G) No gene 14q (45991015) 5 207 1371 1583 0.07 14 339 1545 1898 0.10 0.326 0.69 (0.58~0.82) 2.03E-05rs2158214 (T/G) No gene 7q (125319892) 461 763 359 1583 0.47 647 921 330 1898 0.42 0.942 1.23 (1.12~1.35) 2.09E-05rs9416286 (T/C) No gene 10q (55059036) 549 755 279 1583 0.41 777 857 263 1897 0.36 0.279 1.23 (1.12~1.37) 2.34E-05rs10514036 (A/G) No gene 18q (67894269) 865 620 98 1583 0.26 917 807 171 1895 0.30 0.730 0.80 (0.72~0.88) 2.48E-05rs260633 (T/C) EDAR 2q (108891962) 1061 472 49 1582 0.18 1393 467 38 1898 0.14 0.875 1.32 (1.16~1.49) 2.50E-05rs7837328 (A/G) No gene 8q (128492309) 209 750 624 1583 0.37 189 842 867 1898 0.32 0.458 1.23 (1.12~1.36) 2.79E-05

p Value‡SNP Gene OR (95% CI)†Case Control

SNPs were ranked according to their p Value in the screening stage of colorectal cancer. OR, Odds ratio; CI, confidence interval. ||Significance level for the departures from Hardy Weinberg equilibrium (HWE) in the control samples. †OR of minor allele from 2x2 allele frequency table. ‡p Values derived from Cochran-Armitage trend tests. Chromosomal positions are from NCBI build 36.

Supplementary Table 2 The results of screening stage analysis of colorectal cancer

Page 3: Supplementary Table  1

Allele Chromosome Case Control p Value(1/2) (position) 11 12 22 SUM MAF 11 12 22 SUM MAF (HWE)||

rs7988900 (T/C) No gene 13q (97276536) 583 375 67 1025 0.25 888 831 176 1895 0.31 0.356 0.73 (0.65~0.82) 2.71E-07rs12412826 (A/G) APBB1IP 10p (26818612) 15 229 781 1025 0.13 10 312 1576 1898 0.09 0.194 1.52 (1.27~1.79) 2.04E-06rs3101357 (T/G) FRMD4A 10p (14159726) 435 473 117 1025 0.34 972 768 158 1898 0.29 0.717 1.32 (1.18~1.47) 2.71E-06rs11003722 (A/G) No gene 10q (55064621) 138 465 422 1025 0.36 190 760 948 1898 0.30 0.040 1.32 (1.18~1.48) 2.82E-06rs2049339 (T/G) BBX 3q (108954389) 842 174 9 1025 0.09 1673 220 5 1898 0.06 0.427 1.60 (1.32~1.96) 2.92E-06rs11847817 (T/C) No gene 14q (38089551) 548 402 75 1025 0.27 1167 645 86 1898 0.22 0.794 1.34 (1.19~1.52) 3.28E-06rs9875732 (T/C) BBX 3q (108944421) 842 174 9 1025 0.09 1671 222 5 1898 0.06 0.403 1.59 (1.30~1.92) 4.35E-06rs2614143 (A/G) FRMD4A 10p (14163465) 433 472 120 1025 0.35 964 771 163 1898 0.29 0.616 1.31 (1.16~1.47) 4.39E-06rs2158214 (T/G) No gene 7q (125319892) 285 499 241 1025 0.48 647 921 330 1898 0.42 0.942 1.29 (1.15~1.43) 5.84E-06rs4841926 (T/C) COL5A1 9q (136741106) 413 449 163 1025 0.38 576 979 343 1898 0.44 0.039 0.78 (0.70~0.87) 7.07E-06rs10238157 (A/G) No gene 7q (125324655) 439 449 137 1025 0.35 956 766 176 1898 0.29 0.209 1.31 (1.16~1.47) 7.22E-06rs5759225 (A/G) SCUBE1 22q (41970672) 607 342 76 1025 0.24 1238 596 64 1898 0.19 0.453 1.35 (1.18~1.54) 8.43E-06rs10825073 (T/C) No gene 10q (55041607) 104 435 486 1025 0.31 151 679 1068 1898 0.26 0.004 1.32 (1.17~1.48) 1.13E-05rs1403774 (T/G) BBX 3q (108962444) 23 324 678 1025 0.18 40 442 1416 1898 0.14 0.426 1.39 (1.19~1.6) 1.13E-05rs6428571 (T/C) No gene 1p (90373522) 8 128 889 1025 0.07 28 346 1524 1898 0.11 0.104 0.64 (0.52~0.78) 1.19E-05rs6481026 (A/G) No gene 10q (55041794) 104 434 486 1024 0.31 151 679 1068 1898 0.26 0.004 1.32 (1.16~1.47) 1.22E-05rs3128591 (A/G) COL5A1 9q (136741940) 413 448 164 1025 0.38 580 977 341 1898 0.44 0.045 0.78 (0.70~0.88) 1.45E-05rs6782394 (A/G) BBX 3q (108881819) 742 268 15 1025 0.15 1519 352 27 1898 0.11 0.204 1.42 (1.20~1.67) 1.64E-05rs6789529 (T/C) BBX 3q (108887391) 669 334 22 1025 0.18 1400 457 41 1898 0.14 0.607 1.37 (1.18~1.59) 1.68E-05rs7078645 (A/G) No gene 10q (55065324) 347 492 186 1025 0.42 784 849 265 1898 0.36 0.150 1.28 (1.15~1.43) 1.70E-05rs3935335 (A/G) COL5A1 9q (136735987) 410 449 166 1025 0.38 575 971 344 1890 0.44 0.061 0.79 (0.70~0.88) 1.85E-05rs7906396 (T/C) No gene 10q (55061615) 346 492 187 1025 0.42 780 852 266 1898 0.36 0.175 1.27 (1.14~1.43) 1.90E-05rs2415493 (A/G) No gene 14q (38122872) 161 536 328 1025 0.42 244 887 765 1896 0.36 0.599 1.27 (1.13~1.41) 1.99E-05rs11835096 (A/G) No gene 12q (114526338) 663 328 33 1024 0.19 1087 709 102 1898 0.24 0.327 0.75 (0.66~0.86) 2.04E-05rs4240703 (A/G) COL5A1 9q (136735749) 165 447 413 1025 0.38 339 978 581 1898 0.44 0.038 0.79 (0.71~0.88) 2.21E-05rs11003740 (A/C) No gene 10q (55088093) 341 493 191 1025 0.43 755 882 261 1898 0.37 0.894 1.27 (1.14~1.41) 2.26E-05rs10511753 (A/G) No gene 9p (25276650) 14 221 790 1025 0.12 26 275 1597 1898 0.09 0.005 1.47 (1.23~1.75) 2.33E-05

p Value‡SNP Gene OR (95% CI)†

SNPs were ranked according to their p Value in the screening stage of colon cancer. OR, Odds ratio; CI, confidence interval. ||Significance level for the departures from Hardy Weinberg equilibrium (HWE) in the control samples. †OR of minor allele from 2x2 allele frequency table. ‡ p Values derived from Cochran-Armitage trend tests. Chromosomal positions are from NCBI build 36.

Supplementary Table 3 The results of screening stage analysis of colon cancer

Page 4: Supplementary Table  1

Allele Chromosome Case Control p Value(1/2) (position) 11 12 22 SUM MAF 11 12 22 SUM MAF (HWE)||

rs6789529 (T/C) BBX 3q (108887391) 248 152 10 410 0.21 1400 457 41 1898 0.14 0.607 1.61 (1.33~1.96) 9.32E-07rs11785575 (A/G) No gene 8p (37280959) 38 167 205 410 0.30 87 655 1156 1898 0.22 0.636 1.51 (1.27~1.78) 1.66E-06rs6782394 (A/G) BBX 3q (108881819) 280 124 6 410 0.17 1519 352 27 1898 0.11 0.204 1.67 (1.35~2.04) 2.14E-06rs1403774 (T/G) BBX 3q (108962444) 9 147 254 410 0.20 40 442 1416 1898 0.14 0.426 1.58 (1.30~1.92) 3.09E-06rs6779452 (A/G) BBX 3q (108881301) 10 148 252 410 0.20 40 455 1403 1898 0.14 0.663 1.57 (1.30~1.90) 3.34E-06rs2049339 (T/G) BBX 3q (108954389) 327 80 3 410 0.10 1673 220 5 1898 0.06 0.427 1.82 (1.41~2.38) 4.26E-06rs1996041 (A/G) No gene 12p (28649901) 42 211 157 410 0.36 371 949 578 1898 0.45 0.600 0.70 (0.60~0.82) 5.28E-06rs9875732 (T/C) BBX 3q (108944421) 327 80 3 410 0.10 1671 222 5 1898 0.06 0.403 1.79 (1.39~2.33) 5.83E-06rs4729566 (A/G) ZKSCAN1 7q (99452249) 190 169 51 410 0.33 649 918 331 1898 0.42 0.837 0.69 (0.59~0.81) 6.83E-06rs9848674 (A/C) BBX 3q (108884573) 274 130 6 410 0.17 1489 378 31 1898 0.12 0.218 1.59 (1.30~1.96) 7.58E-06rs1888871 (A/G) No gene 9p (32876639) 42 198 170 410 0.34 131 756 1011 1898 0.27 0.520 1.43 (1.22~1.68) 9.88E-06rs2163059 (A/G) XDH 2p (31456638) 114 209 87 410 0.47 716 906 276 1898 0.38 0.698 1.41 (1.20~1.64) 9.99E-06rs9809990 (A/G) MDS1 3q (170354088) 51 198 161 410 0.37 150 797 950 1897 0.29 0.337 1.42 (1.21~1.66) 1.17E-05rs234460 (A/G) No gene 14q (96919715) 174 179 57 410 0.36 993 749 156 1898 0.28 0.379 1.43 (1.22~1.69) 1.23E-05rs7988900 (T/C) No gene 13q (97276536) 243 141 26 410 0.24 888 831 176 1895 0.31 0.356 0.68 (0.57~0.81) 1.24E-05rs4790657 (T/G) FLJ42461 17p (4455025) 66 212 132 410 0.42 475 956 467 1898 0.50 0.747 0.72 (0.62~0.83) 1.57E-05rs11710737 (A/G) BBX 3q (108946860) 259 142 9 410 0.20 1419 438 41 1898 0.14 0.296 1.54 (1.25~1.85) 2.04E-05rs10238157 (A/G) No gene 7q (125324655) 161 194 55 410 0.37 956 766 176 1898 0.29 0.209 1.41 (1.20~1.64) 2.28E-05rs10450689 (T/C) No gene 12p (28685330) 142 217 49 408 0.39 547 927 423 1897 0.47 0.421 0.71 (0.61~0.83) 2.29E-05rs4949290 (A/G) LAPTM5 1p (30976447) 23 173 214 410 0.27 75 613 1210 1898 0.20 0.810 1.45 (1.22~1.72) 2.36E-05

p Value‡SNP Gene OR (95% CI)†

SNPs were ranked according to their p Value in the screening stage of proximal colon cancer. OR, Odds ratio; CI, confidence interval. ||Significance level for the departures from Hardy Weinberg equilibrium (HWE) in the control samples. †OR of minor allele from 2x2 allele frequency table. ‡ p Values derived from Cochran-Armitage trend tests. Chromosomal positions are from NCBI build 36.

Supplementary Table 4 The results of screening stage analysis of proximal colon cancer

Page 5: Supplementary Table  1

Allele Chromosome p Value(1/2) (position) 11 12 22 SUM MAF 11 12 22 SUM MAF (HWE)||

rs7758229 (T/G) SLC22A3 6q (160760242) 53 232 292 577 0.29 97 641 1156 1894 0.22 0.506 1.46 (1.26~1.70) 5.58E-07rs1427667 (T/C) No gene 2q (218602372) 406 157 16 579 0.16 1511 362 25 1898 0.11 0.531 1.61 (1.33~1.92) 7.57E-07rs2039645 (A/G) TRPM3 9q (72642107) 34 202 343 579 0.23 55 544 1299 1898 0.17 0.830 1.46 (1.24~1.71) 3.52E-06rs3101357 (T/G) FRMD4A 10p (14159726) 237 271 71 579 0.36 972 768 158 1898 0.29 0.717 1.39 (1.20~1.59) 4.25E-06rs2275242 (T/C) TRPM3 9q (72637875) 34 202 343 579 0.23 55 546 1297 1898 0.17 0.787 1.46 (1.24~1.71) 4.30E-06rs12412826 (A/G) APBB1IP 10p (26818612) 8 137 434 579 0.13 10 312 1576 1898 0.09 0.194 1.59 (1.30~1.95) 5.71E-06rs2614143 (A/G) FRMD4A 10p (14163465) 237 269 73 579 0.36 964 771 163 1898 0.29 0.616 1.37 (1.19~1.59) 7.96E-06rs10262428 (T/G) No gene 7q (80408078) 114 274 191 579 0.57 475 977 446 1898 0.49 0.195 1.35 (1.18~1.54) 8.97E-06rs10975258 (A/C) KIAA1432 9p (5709116) 305 220 54 579 0.28 1159 643 96 1898 0.22 0.578 1.40 (1.20~1.64) 1.18E-05rs7580997 (T/C) No gene 2q (218591431) 422 144 13 579 0.15 1538 339 21 1898 0.10 0.633 1.54 (1.27~1.89) 1.24E-05rs4841926 (T/C) COL5A1 9q (136741106) 235 262 82 579 0.37 576 979 343 1898 0.44 0.039 0.75 (0.65~0.85) 1.52E-05rs11745068 (T/G) No gene 5q (134503393) 156 291 132 579 0.48 686 881 331 1898 0.41 0.098 1.35 (1.18~1.54) 1.55E-05rs2457571 (T/C) SLC22A3 6q (160754818) 78 288 213 579 0.38 197 801 895 1893 0.32 0.371 1.35 (1.18~1.55) 1.91E-05rs888934 (A/G) No gene 5q (169856310) 9 125 445 579 0.12 53 562 1283 1898 0.18 0.361 0.60 (0.54~0.80) 2.11E-05rs9364554 (T/C) SLC22A3 6q (160753654) 78 287 214 579 0.38 197 800 897 1894 0.32 0.348 1.35 (1.17~1.54) 2.17E-05rs5759225 (A/G) SCUBE1 22q (41970672) 338 194 47 579 0.25 1238 596 64 1898 0.19 0.453 1.41 (1.20~1.64) 2.20E-05rs3128591 (A/G) COL5A1 9q (136741940) 235 262 82 579 0.37 580 977 341 1898 0.44 0.045 0.75 (0.65~0.86) 2.35E-05rs3935335 (A/G) COL5A1 9q (136735987) 234 262 83 579 0.37 575 971 344 1890 0.44 0.061 0.75 (0.65~0.85) 2.38E-05

p Value‡ OR (95% CI)†SNP Case ControlGene

Supplementary Table 5 The results of screening stage analysis of distal colon cancer

SNPs were ranked according to their p Value in the screening stage of distal colon cancer. OR, Odds ratio; CI, confidence interval. ||Significance level for the departures from Hardy Weinberg equilibrium (HWE) in the control samples. †OR of minor allele from 2x2 allele frequency table. ‡p Values derived from Cochran-Armitage trend tests. Chromosomal positions are from NCBI build 36.

Page 6: Supplementary Table  1

Allele Chromosome Case Control p Value(1/2) (position) 11 12 22 SUM MAF 11 12 22 SUM MAF (HWE)||

rs6942273 (A/G) CDKAL1 6p (21333556) 239 215 43 497 0.30 744 867 287 1898 0.38 0.189 0.71 (0.61~0.83) 9.52E-06rs10792847 (A/G) C11orf73 11q (85731067) 28 140 329 497 0.20 125 757 1016 1898 0.27 0.313 0.68 (0.57~0.81) 1.09E-05rs17697705 (A/G) No gene 16q (64460451) 151 234 112 497 0.54 393 965 540 1898 0.46 0.316 1.37 (1.19~1.57) 1.14E-05rs2908866 (C/T) No gene 16q (47608882) 16 168 312 496 0.20 32 491 1375 1898 0.15 0.115 1.47 (1.23~1.76) 1.41E-05rs901779 (A/G) GUCY1A2 11q (106162073) 29 205 263 497 0.26 78 611 1209 1898 0.20 0.942 1.42 (1.21~1.67) 1.77E-05rs3847009 (A/G) No gene 7p (33117706) 236 213 48 497 0.31 730 873 295 1898 0.39 0.205 0.72 (0.62~0.83) 1.91E-05rs7837328 (A/G) No gene 8q (128492309) 73 244 180 497 0.39 189 842 867 1898 0.32 0.458 1.36 (1.18~1.58) 2.13E-05rs2054129 (C/T) No gene 4p (34723412) 370 115 12 497 0.14 1572 300 26 1898 0.09 0.008 1.59 (1.28~1.96) 2.26E-05rs10142229 (C/T) TDRD9 14q (103534562) 1 56 440 497 0.06 24 341 1532 1897 0.10 0.311 0.54 (0.41~0.72) 2.45E-05

p Value‡SNP Gene OR (95% CI)†

Supplementary Table 6 The results of screening stage analysis of rectal cancer

SNPs were ranked according to their p Value in the screening stage of rectal cancer. OR, Odds ratio; CI, confidence interval. ||

Significance level for the departures from Hardy Weinberg equilibrium (HWE) in the control samples. †OR of minor allele from 2x2 allele frequency table. ‡p Values derived from Cochran-Armitage trend tests. Chromosomal positions are from NCBI build 36.

Page 7: Supplementary Table  1

Allele Case Control(1/2) 11 12 22 SUM MAF 11 12 22 SUM MAF

novel v1 (A/G) 160689757 1908 6 0 1914 0.00 1809 7 0 1816 0.00 0.81 (0.27-2.44) 7.09E-01rs668871 (T/C) 160689801 149 738 1027 1914 0.27 163 766 886 1815 0.30 0.86 (0.78-0.95) 4.11E-03rs9346816 (A/G) 160702652 233 781 901 1915 0.33 244 779 794 1817 0.35 0.90 (0.82-0.99) 4.11E-02rs1018234 (T/C) 160716048 248 852 816 1916 0.35 282 866 668 1816 0.39 0.84 (0.76-0.92) 2.00E-04rs884742 (A/C) 160727422 730 903 280 1913 0.38 600 883 335 1818 0.43 0.83 (0.76-0.91) 8.71E-05novel v2 (T/C) 160748108 0 39 1876 1915 0.01 0 42 1776 1818 0.01 0.88 (0.57-1.36) 5.66E-01rs7745775 (T/G) 160753458 1046 740 130 1916 0.26 1002 694 121 1817 0.26 0.98 (0.89-1.09) 7.38E-01rs9364554 (T/C) 160753654 232 896 788 1916 0.35 190 765 861 1816 0.32 1.19 (1.09-1.32) 2.92E-04rs2457571 (T/C) 160754818 208 865 843 1916 0.33 189 768 859 1816 0.32 1.09 (0.99-1.2) 8.42E-02rs7758229 (T/G) 160760242 145 738 1032 1915 0.27 93 615 1108 1816 0.22 1.30 (1.17-1.44) 1.96E-06rs3123636 (T/C) 160762527 1033 738 145 1916 0.27 1108 615 93 1816 0.22 1.30 (1.16-1.45) 2.09E-06rs4708867 (A/G) 160762715 1371 501 43 1915 0.15 1324 449 44 1817 0.15 0.96 (0.84-1.09) 5.08E-01rs2665357 (A/C) 160768157 354 929 631 1914 0.43 405 907 506 1818 0.47 0.84 (0.76-0.91) 1.14E-04rs3106164 (T/C) 160770263 184 813 919 1916 0.31 138 691 988 1817 0.27 1.23 (1.11-1.36) 6.82E-05rs4709432 (A/G) 160773919 1102 703 111 1916 0.24 1014 695 108 1817 0.25 0.95 (0.85-1.05) 3.49E-01rs8187725 (T/C) 160778144 0 0 1915 1915 0.00 0 1 1816 1817 0.00 -- 3.05E-01novel v3 (T/C) 160783877 0 18 1896 1914 0.00 0 12 1805 1817 0.00 1.43 (0.69-2.96) 3.38E-01rs1810126 (T/C) 160792141 457 979 478 1914 0.49 406 919 491 1816 0.48 1.07 (0.98-1.18) 1.18E-01rs3088442 (A/G) 160792642 456 981 476 1913 0.49 400 912 499 1811 0.47 1.09 (1.00-1.20) 5.42E-02rs1050898 (T/C) 160792727 0 0 1912 1912 0.00 0 1 1816 1817 0.00 -- 3.05E-01rs2076828 (C/G) 160792776 457 979 477 1913 0.49 404 912 496 1812 0.47 1.08 (0.99-1.19) 7.94E-02rs41267803 (A/C) 160792998 0 1 1913 1914 0.00 0 1 1817 1818 0.00 0.95 (0.06-15.19) 9.71E-01

p Value‡SNP Position OR (95% CI)†

Supplementary Table 7 SNPs mapping to SLC22A3 along with p Value obtained from Cochran-Armitage trend tests

OR, Odds ratio; CI, confidence interval. †OR of minor allele from 2x2 allele frequency table. ‡p Values derived from Cochran-Armitage trend tests. Chromosomal positions are from NCBI build 36.

Page 8: Supplementary Table  1

Forward primers Reverse primersexon1 CGGCGGAGTAAAGAGAGG CTGGGAGCCAGCATCGexon2 CCTTTGCAGTTATTTAAACAAAGGAT CATAAAACATTTTTCTCCCCGTAexon3 ATTTTCCCATTGTGTTGAAGAAA ACATGAGGAAGAGGAAGGTTGAexon4 GTGGAAGCCTCCGTATCTGA TTTCATTTTCATGTCTGTTTGGAexon5 CCCCATCCATTATAACCTTGC CAACAAAATCAATTCACCAGCTTexon6 TGAAAGCCCCTAGTCACTTCAG CGCTTGTGAACCTGTAGCAAexon7 TCCCTTCCTTCAAATCAGCTT TGATTCCATTGCACATTTCCexon8 GGAGGCCACTAAGCAAATACT TGAGCTAAGGAAACGACTTCAexon9 CTTCACACTTCCTTTGGTTTTT TTGGCTCTCAAAACTGAAATAGTexon10 ATTGATCTGGGATGCAGAGG CCCTGTGGATATTCAATTTTCTexon11 TGGGTTTTCATGAATGTATTTGA GATGTAGCTGAAATGCACACG

Supplementary Table 9 List of primers used for SNP discovery

List of optimal primer sequences as designed with Primer3.

OR, Odds ratio; CI, confidence interval. †OR of minor allele from 2x2 allele frequency table. ‡p Values derived from Cochran-Armitage trend tests. || Minor allele frequency of control samples in the screening stage. ¶ Minor allele frequency of healthy control samples in the screening stage. Chromosomal positions are from NCBI build 36.

Supplementary Table 8 The results of previously reported loci in screening stage Allele Chromosome(1/2) (position) OR (95% CI)† p Value‡ MAF|| OR (95% CI)† p Value‡ MAF¶

rs6983267 (T/G) No gene 8q (128482487) 1.25 (1.12~1.37) 1.08E-05 0.34 1.18 (1.04-1.33) 7.55E-03 0.35rs10795668 (A/G) No gene 10p (8741225) 0.90 (0.81~0.99) 2.47E-02 0.41 0.93 (0.83-1.05) 2.26E-01 0.40rs3802842 (A/C) No gene 11q (110676919) 1.06 (0.96~1.18) 2.31E-01 0.34 1.03 (0.91-1.16) 6.48E-01 0.35rs4444235 (T/C) BMP4 14q (53480669) 0.95 (0.86~1.05) 3.22E-01 0.40 0.95 (0.84-1.07) 3.79E-01 0.40rs4779584 (T/C) No gene 15q (30782048) 1.03 (0.91~1.18) 6.07E-01 0.17 1.06 (0.91-1.23) 4.75E-01 0.17rs9929218 (A/G) CDH1 16q (67378447) 1.01 (0.89~1.14) 8.99E-01 0.17 1.04 (0.89-1.21) 6.54E-01 0.17rs4939827 (T/C) SMAD7 18q (44707461) 1.25 (1.12~1.40) 9.54E-05 0.20 1.28 (1.11-1.48) 5.01E-04 0.20rs10411210 (T/C) RHPN2 19q (38224140) 0.93 (0.81~1.06) 2.78E-01 0.15 0.90 (0.76-1.05) 1.93E-01 0.16rs961253 (A/C) No gene 20p (6352281) 1.05 (0.90~1.21) 5.33E-01 0.11 1.02 (0.86-1.23) 7.93E-01 0.12

Screening stage (Number of Cont: 904)Screening stage (Number of Cont: 1898)SNP Gene

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Allele(1/2) 11 12 22 11 12 22

Screening stage 84 375 564 97 641 1156 1.28 (1.13~1.45) 1.49E-04First replication 108 582 926 96 603 1077 1.14 (1.02~1.27) 2.71E-02Second replication 60 323 471 33 295 490 1.24 (1.05~1.45) 8.44E-03Meta-analysis|| 1.21 (1.12~1.30) 7.40E-07 0.37

Gene StageCase Control

OR (95%CI)† p Value‡ p Heterogeneity§

rs7758229 (T/G) SLC22A3

SNP

OR, Odds ratio; CI, confidence interval. † OR of minor allele from 2 x 2 allele frequency table. ‡ p Values derived from Cochran-Armitage trend tests. § Result of Breslow-Day test. || Meta-analysis of all three studies. Odds ratio and p Values for independence test were calculated by Mantel-Haenzel method.

Supplementary Table 10 Results of replication studies and meta-analysis for colon cancer in Japanese

Allele(1/2) 11 12 22 11 12 22

Screening stage 113 570 897 97 641 1156 1.19 (1.07-1.33) 2.39E-03First replication 195 1119 1782 96 603 1077 1.12 (1.01-1.23) 2.78E-02Second replication 108 532 845 33 295 490 1.19 (1.03-1.37) 1.88E-02Meta-analysis|| 1.16 (1.08-1.23) 1.31E-05 0.64

OR (95%CI)† p Value‡ p Heterogeneity§

rs7758229 (T/G) SLC22A3

SNP Gene StageCase Control

OR, Odds ratio; CI, confidence interval. † OR of minor allele from 2 x 2 allele frequency table. ‡ p Values derived from Cochran-Armitage trend tests. § Result of Breslow-Day test. || Meta-analysis of all three studies. Odds ratio and p Values for independence test were calculated by Mantel-Haenzel method.

Supplementary Table 11 Results of replication studies and meta-analysis for colorectal cancer in Japanese