Table 2

Discovered loci with weak effects on colorectal cancer susceptibility

Locus (reference)Independent index SNP*Risk alleleRAF†OR (95% CI)Smallest p valueGenomic positionClosest genePutative gene target‡Distance to putative target
Loci discovered by genome wide association studies with independent replication and p values <5×10−8
 1q25.370 71rs10911251A0.541.09 (1.06 to 1.12)2×10−8IntronLAMC1LAMC133 kb
 1q4163rs6687758G0.221.09 (1.06 to 1.12)2×10−9Intergenic6.6 kb 3′ of RP11DUSP10249 kb
 2q32.370rs11903757C0.161.16 (1.10 to 1.22)4×10−8Intergenic34 kb 3′ of NABP1MYO1B297 kb
 3p14.172rs812481G0.581.09 (1.05 to 1.11)2×10−8IntronLRIG1LRIG1In gene
 3p22.172rs35360328A0.161.14 (1.09 to 1.19)3×10−9Intergenic21 kb 3′ of RP11CTNNB1316 kb
 3q26.263rs10936599C0.751.04 (1.04 to 1.10)3×10−8SynonymousMYNNTERC9 kb
 5q31.173rs647161A0.661.06 (1.02 to 1.11)4×10−10IntergenicPITX1PITX1130 kb
 6p2174rs1321311A0.201.10 (1.07 to 1.13)1×10−10IntergenicCDKN1ACDKN1A32 kb
 6q25.375rs7758229T0.321.28 (1.18 to 1.39)8×10−9IntronSLC22A3SLC22A2160 kb
 8q23.361rs16892766C0.091.27 (1.20 to 1.34)3×10−18Intergenic24 kb 3′ of EIF3HEIF3H24 kb
 8q24.2157 59 61 70 75–77rs6983267G0.481.19 (1.15 to 1.23)9×10−26IntergenicMYC393 kb
 9p2457 78rs719725A0.601.14 (1.05 to 1.15)1×10−5Intergenic34 kb 3′ of TPD52L3TPD52L3 or UHRF234 kb
 10p1461rs10795668G0.671.12 (1.10 to 1.16)3×10−13Intergenic2.4 kb 5′ of RN5S299GATA3584 kb
 10q22.379rs704017G0.581.10 (1.06 to 1.13)2×10−8IntronRP11.1ZMIZ1 or AS110 kb
 10q24.271rs1035209T0.201.12 (1.08 to 1.16)4×10−11Intergenic16 kb 5′ of snoU13NKX2–349 kb
 10q25.280rs12241008C0.091.19 (1.12 to 1.26)3×10−8IntronVTI1AVTI1AIn gene
 10q25.279rs11196172A0.111.14 (1.10 to 1.18)1×10−12IntronTCF7L2TCF7L2In gene
 11q12.279rs1535A0.641.09 (1.04 to 1.13)8×10−20IntronFADS1FEN134 kb
 11q13.474rs3824999C0.531.08 (1.05 to 1.10)4×10−10IntronPOLD3POLD3In gene
 11q2359rs3802842C0.271.11 (1.08 to 1.15)6×10−10IntronCOLCA2COLCA2In gene
 12p13.3179rs10849432T0.911.14 (1.09 to 1.18)3×10−10Intergenic34 kb 5′ of PLEKHG6CD941 kb
 12p13.3270 71rs3217810T0.121.10 (1.06 to 1.14)2×10−10IntronCCND2CCND2In gene
 12p13.3273rs10774214T0.381.17 (1.11 to 1.23)5×10−10IntronCCND2CCND2In gene
 12q13.1276rs11169552C0.751.09 (1.05 to 1.11)2×10−10Intergenic1.8 kb 5′ of ATF1ATF11.8 kb
 12q13.1363rs7136702T0.331.06 (1.04 to 1.08)4×10−8Intergenic6.4 kb 3′ of LARP4DIP2BIn gene
 12q24.1272rs3184504C0.531.09 (1.06 to 1.12)2×10−8MissenseSH2B3SH2B3In gene
 12q24.2272rs73208120G0.111.16 (1.11 to 1.23)3×10−8IntronNOS1NOS1In gene
 14q22.264rs1957636A0.411.08 (1.06 to 1.11)1×10−9Intergenic135 kb 5′ of BMP4BMP4139 kb
 14q22.261 62rs4444235C0.481.11 (1.08 to 1.15)8×10−10Intergenic4.2 kb 3′ of MIR5580BMP45 kb
 15q1360 61 66 70rs4779584T0.191.35 (1.14 to 1.60)4×10−14Intergenic5.5 kb 3′ of SCG5GREM128 kb
 16q22.162rs9929218G0.711.10 (1.06 to 1.12)1×10−8IntronCDH1CDH1In gene
 17p13.379rs12603526C0.261.10 (1.06 to 1.14)3×10−8IntronNXNNXNIn gene
 18q2158 59rs4939827T0.531.20 (1.16 to 1.24)8×10−28IntronSMAD7SMAD7In gene
 18q2181rs7229639A0.161.22 (1.15 to 1.29)3×10−11IntronSMAD7SMAD7In gene
 19q13.162rs10411210C0.901.15 (1.10 to 1.20)5×10−9IntronRHPN2RHPN2In gene
 19q13.279rs1800469G0.691.09 (1.06 to 1.12)1×10−8IntronTMEM91TGFB1465
 20p12.364 73rs2423279C0.261.10 (1.06 to 1.14)7×10−9Intergenic51 kb 3′ of HAO1BMP21 Mb
 20p12.364 66rs4813802G0.341.10 (1.06 to 1.12)7×10−11Intergenic12 kb 3′ of RP5-859D4.3BMP249 kb
 20p12.3rs961253A0.371.12 (1.08 to 1.16)2×10−10Intergenic23 kb 5′ of RP11-199O14.1BMP2344 kb
 20q13.172rs6066825G0.361.09 (1.06 to 1.12)4×10 −9IntronPREX1PREX1In gene
 20q13.3363 66rs4925386C0.681.08 (1.05 to 1.10)2×10−10IntronLAMA5LAMA5In gene
 Xp22.274rs5934683C0.621.07 (1.04 to 1.10)7×10−10IntergenicGPR143SHROOM2129 kb
Loci discovered in candidate gene studies with cumulative evidence from subsequent meta-analysis considered to be strong
 3p22.254rs1800734¶A0.261.51 (1.34 to 1.69)7×10−125′UTRMLH1MLH1In gene
 5q22.2APC I1307KA0.06**2.17 (1.64 to 2.86)<0.05MissenseAPCAPCIn gene
 22q12.154rs17879961C0.041.56 (1.32 to 1.84)1×10−7§MissenseCHEK2CHEK2In gene
  • *When more than one correlated variants (D′<0.5) is identified the most significant SNP across 21 GWAS studies is reported.

  • †Risk allele frequency (RAF) from 1000 Genomes Project June 2011 release (European frequency is based on CEU+FIN+GBR+IBS+TSI and Asian frequency is based on CHB+CHS+JPT) when frequency was not reported from study control population.

  • ‡For loci with hypothesized regulatory potential the target gene was predicted using publicly available data and review of literature for: 1. allelic expression assays such as luciferase, 2. electromobility shift assays, 3. Roadmap activity assays in colorectal mucosa tissues, 4. chromatin capture in CRC cell lines, and 5. pathway analysis.

  • §Evidence from meta-analysis and candidate approaches is compelling but does not reach genome-wide threshold.

  • ¶Association observed in proximal colon.

  • **Observed risk allele frequency in Ashkenazim.