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. 2019 Aug 20;11(8):1954. doi: 10.3390/nu11081954

Table 4.

P-values of pathway- and gene-level associations with CRC risk overall and by tumor location (colon vs. rectal) and of interactions with 25(OH)D concentrations (per 24.96 nmol/L), the EPIC study, 1992–2003.

Pathway/Gene No. of SNPs No. of SNPs Retained After Pruning Colorectal Cancer Colon Cancer Rectal Cancer
Gene or Pathway Only Gene- or Pathway-25(OH)D Interaction Gene or Pathway Only Gene- or Pathway-25(OH)D Interaction Gene or Pathway Only Gene- or Pathway-25(OH)D Interaction
P PBH a P PBH P PBH P PBH P PBH P PBH
Vitamin D metabolism 276 245 0.580 0.159 0.550 0.160 0.418 0.116
Identified in GWAS of 25(OH)D b 2 2 0.235 0.759 0.867 0.999 0.167 0.657 0.923 0.990 0.561 0.944 0.499 0.991
CUBN 116 106 0.173 0.741 0.764 0.999 0.130 0.657 0.896 0.990 0.083 0.470 0.490 0.991
CYP24A1 25 23 0.443 0.777 0.358 0.999 0.083 0.647 0.666 0.990 0.622 0.944 0.007 0.595
CYP27A1 5 5 0.500 0.777 0.299 0.999 0.488 0.819 0.086 0.522 0.968 0.968 0.256 0.991
CYP27B1 6 5 0.448 0.777 0.037 0.446 0.585 0.829 0.041 0.448 0.514 0.944 0.154 0.991
CYP2R1 12 9 0.115 0.741 0.811 0.999 0.368 0.815 0.921 0.990 0.044 0.459 0.727 0.991
CYP3A4 7 5 0.241 0.759 0.730 0.999 0.461 0.815 0.533 0.990 0.262 0.747 0.392 0.991
DHCR7 12 6 0.997 0.997 0.549 0.999 0.800 0.911 0.614 0.990 0.434 0.944 0.716 0.991
GC 24 20 0.484 0.777 0.018 0.406 0.912 0.954 0.026 0.442 0.241 0.747 0.316 0.991
LRP2 67 64 0.804 0.926 0.377 0.999 0.508 0.819 0.677 0.990 0.904 0.967 0.487 0.991
Mineral homeostasis 58 40 0.834 0.313 0.912 0.431 0.537 0.782
CASR 31 23 0.580 0.784 0.736 0.999 0.536 0.819 0.957 0.990 0.643 0.944 0.565 0.991
PTH 6 5 0.931 0.982 0.671 0.999 0.773 0.911 0.739 0.990 0.539 0.944 0.736 0.991
CALB1 2 2 0.489 0.777 0.741 0.999 0.400 0.815 0.847 0.990 0.882 0.967 0.819 0.991
TRPV5 9 7 0.657 0.846 0.054 0.456 0.920 0.954 0.081 0.522 0.337 0.818 0.225 0.991
TRPV6 10 3 0.263 0.777 0.880 0.999 0.520 0.819 0.954 0.990 0.112 0.595 0.713 0.991
VDR complex/Transcriptional Co-regulators and Co-activators 538 490 0.634 0.041 0.874 0.105 0.180 0.727
ACTL6A 3 3 0.239 0.759 0.395 0.999 0.262 0.815 0.497 0.990 0.506 0.944 0.613 0.991
ARID1A 8 7 0.408 0.777 0.032 0.446 0.306 0.815 0.048 0.448 0.133 0.628 0.068 0.924
BAZ1B 14 9 0.478 0.777 0.955 0.999 0.360 0.815 0.867 0.990 0.385 0.909 0.935 0.993
CARM1 4 4 0.641 0.839 0.006 0.406 0.831 0.929 0.022 0.442 0.290 0.747 0.120 0.991
CHAF1A 5 4 0.035 0.511 0.013 0.406 0.307 0.815 0.047 0.448 0.007 0.187 0.098 0.926
CREBBP 15 12 0.388 0.777 0.285 0.999 0.800 0.911 0.215 0.865 0.011 0.187 0.793 0.991
EP300 6 5 0.771 0.926 0.791 0.999 0.434 0.815 0.835 0.990 0.917 0.967 0.342 0.991
HDAC9 149 141 0.559 0.784 0.873 0.999 0.524 0.819 0.578 0.990 0.553 0.944 0.970 0.993
MED1 5 5 0.507 0.777 0.561 0.999 0.719 0.899 0.694 0.990 0.131 0.628 0.617 0.991
NCOA1 18 14 0.581 0.784 0.065 0.504 0.804 0.911 0.201 0.854 0.239 0.747 0.355 0.991
NCOA2 19 16 0.542 0.781 0.579 0.999 0.145 0.657 0.456 0.990 0.938 0.967 0.505 0.991
NCOA3 11 9 0.067 0.636 0.051 0.456 0.056 0.647 0.069 0.489 0.522 0.944 0.350 0.991
NCOA7 31 31 0.518 0.777 0.142 0.755 0.646 0.872 0.056 0.448 0.223 0.747 0.482 0.991
NCOR1 7 3 0.312 0.777 0.802 0.999 0.377 0.815 0.759 0.990 0.577 0.944 0.489 0.991
PCAF/KAT2B 31 31 0.801 0.926 0.891 0.999 0.470 0.815 0.865 0.990 0.938 0.967 0.797 0.991
PRMT1 4 4 0.346 0.777 0.351 0.999 0.407 0.815 0.184 0.823 0.618 0.944 0.624 0.991
RXRA 30 27 0.683 0.866 0.763 0.999 0.091 0.647 0.732 0.990 0.662 0.944 0.726 0.991
RXRB 7 3 0.824 0.926 0.074 0.526 0.445 0.815 0.058 0.448 0.617 0.944 0.356 0.991
RXRG 24 24 0.853 0.929 0.716 0.999 0.558 0.819 0.923 0.990 0.875 0.967 0.087 0.924
SMARCA2 1 1 0.506 0.777 0.019 0.406 0.381 0.815 0.012 0.442 0.944 0.967 0.307 0.991
SMARCA4 12 9 0.474 0.777 0.794 0.999 0.559 0.819 0.975 0.990 0.557 0.944 0.923 0.993
SMARCC1 4 4 0.103 0.741 0.893 0.999 0.344 0.815 0.824 0.990 0.082 0.470 0.164 0.991
SMARCD1 3 3 0.312 0.777 0.703 0.999 0.356 0.815 0.550 0.990 0.519 0.944 0.998 0.998
SMARCE1 4 4 0.048 0.582 0.197 0.881 0.191 0.706 0.390 0.990 0.083 0.470 0.059 0.924
SNW1 10 10 0.615 0.816 0.863 0.999 0.740 0.911 0.947 0.990 0.813 0.967 0.807 0.991
SUPT16H 7 6 0.809 0.926 0.990 0.999 0.696 0.899 0.960 0.990 0.663 0.944 0.841 0.991
TOP2B 6 5 0.192 0.741 0.965 0.999 0.097 0.647 0.327 0.990 0.281 0.747 0.400 0.991
NCOR2 62 61 0.701 0.877 0.960 0.999 0.770 0.911 0.609 0.990 0.459 0.944 0.935 0.993
VDR 30 28 0.270 0.777 0.652 0.999 0.372 0.815 0.707 0.990 0.477 0.944 0.706 0.991
TSC2 8 7 0.135 0.741 0.885 0.999 0.354 0.815 0.811 0.990 0.284 0.747 0.761 0.991
TGF-beta signaling 110 98 0.0001 0.616 0.0001 0.729 0.0001 0.342
RHPN2 25 23 0.452 0.777 0.722 0.999 0.144 0.657 0.871 0.990 0.956 0.967 0.701 0.991
SMAD7 23 18 0.0001 0.008 0.927 0.999 0.001 0.043 0.947 0.990 0.0005 0.021 0.627 0.991
SMAD3 39 38 0.0002 0.008 0.367 0.999 0.0001 0.009 0.514 0.990 0.0003 0.021 0.085 0.924
BMP2 5 5 0.016 0.346 0.081 0.527 0.014 0.298 0.224 0.865 0.072 0.470 0.049 0.924
BMP4 1 1 0.201 0.742 0.431 0.999 0.334 0.815 0.615 0.990 0.261 0.747 0.276 0.991
TGFB1 11 8 0.159 0.741 0.293 0.999 0.469 0.815 0.112 0.595 0.068 0.470 0.306 0.991
TGFBR1 4 3 0.950 0.982 0.741 0.999 0.306 0.815 0.838 0.990 0.446 0.944 0.851 0.991
SCG5/GREM1 2 2 0.141 0.741 0.412 0.999 0.170 0.657 0.371 0.990 0.323 0.808 0.656 0.991
Inflammation 133 97 0.888 0.479 0.620 0.156 0.200 0.784
ALOX5 22 11 0.839 0.926 0.264 0.999 0.801 0.911 0.593 0.990 0.782 0.967 0.165 0.991
IL10 13 8 0.462 0.777 0.030 0.446 0.854 0.931 0.006 0.442 0.009 0.187 0.419 0.991
IL10R 9 7 0.734 0.904 0.552 0.999 0.913 0.954 0.751 0.990 0.663 0.944 0.591 0.991
IL2/IL21 6 5 0.441 0.777 0.933 0.999 0.538 0.819 0.978 0.990 0.666 0.944 0.607 0.991
IL6 13 10 0.983 0.995 0.807 0.999 0.982 0.988 0.557 0.990 0.696 0.967 0.843 0.991
IL12B 18 17 0.128 0.741 0.870 0.999 0.079 0.647 0.796 0.990 0.791 0.967 0.761 0.991
IFNG 7 4 0.300 0.777 0.686 0.999 0.453 0.815 0.608 0.990 0.287 0.747 0.497 0.991
TNF 4 4 0.959 0.982 0.218 0.926 0.988 0.988 0.375 0.990 0.790 0.967 0.076 0.924
NFKB1 22 15 0.816 0.926 0.644 0.999 0.873 0.939 0.736 0.990 0.856 0.967 0.794 0.991
IL12A 1 1 0.523 0.777 0.168 0.795 0.452 0.815 0.159 0.770 0.814 0.967 0.706 0.991
IL18 4 4 0.348 0.777 0.514 0.999 0.613 0.840 0.766 0.990 0.182 0.737 0.290 0.991
IL1A/IL1B 11 8 0.951 0.982 0.124 0.701 0.846 0.931 0.054 0.448 0.761 0.967 0.711 0.991
IL8 1 1 0.153 0.741 0.978 0.999 0.060 0.647 0.593 0.990 0.811 0.967 0.669 0.991
RELA (p65) 2 2 0.921 0.982 0.835 0.999 0.938 0.961 0.962 0.990 0.922 0.967 0.690 0.991
Oxidative Stress 51 37 0.726 0.471 0.598 0.460 0.913 0.747
GSR 9 7 0.530 0.777 0.116 0.701 0.712 0.899 0.110 0.595 0.656 0.944 0.376 0.991
GPx2 15 8 0.834 0.926 0.772 0.999 0.713 0.899 0.748 0.990 0.412 0.944 0.915 0.993
TXNRD1 (TR1) 17 14 0.232 0.759 0.859 0.999 0.168 0.657 0.875 0.990 0.757 0.967 0.946 0.993
SOD2 10 8 0.530 0.777 0.374 0.999 0.546 0.819 0.599 0.990 0.896 0.967 0.281 0.991
Insulin growth factor (IGF) signaling 61 52 0.105 0.320 0.550 0.135 0.007 0.346
Associated with IGF levels in GWAS c 4 4 0.414 0.777 0.999 0.999 0.579 0.829 0.901 0.990 0.036 0.437 0.879 0.993
IGF1 17 15 0.131 0.741 0.452 0.999 0.113 0.657 0.668 0.990 0.225 0.747 0.655 0.991
IGF2BP2 3 1 0.303 0.777 0.923 0.999 0.596 0.830 0.580 0.990 0.156 0.698 0.658 0.991
IGFBP2/IGFBP5 24 21 0.187 0.741 0.052 0.456 0.692 0.899 0.018 0.442 0.029 0.411 0.607 0.991
IGFBP3 13 11 0.057 0.601 0.882 0.999 0.273 0.815 0.997 0.997 0.050 0.459 0.058 0.924
Cell Cycle 60 56 0.120 0.852 0.030 0.845 0.482 0.916
KRAS 13 13 0.511 0.777 0.498 0.999 0.262 0.815 0.436 0.990 0.182 0.737 0.925 0.993
FOS (c-fos) 10 9 0.389 0.777 0.425 0.999 0.230 0.815 0.518 0.990 0.764 0.967 0.574 0.991
JUN 7 7 0.569 0.784 0.407 0.999 0.411 0.815 0.163 0.770 0.917 0.967 0.811 0.991
C-MYC region d 13 13 0.010 0.295 0.843 0.999 0.051 0.647 0.857 0.990 0.054 0.459 0.959 0.993
CCND1 4 3 0.177 0.741 0.893 0.999 0.155 0.657 0.565 0.990 0.549 0.944 0.763 0.991
BCL2A1 2 2 0.118 0.741 0.587 0.999 0.083 0.647 0.574 0.990 0.250 0.747 0.915 0.993
BAX 6 5 0.308 0.777 0.892 0.999 0.155 0.657 0.748 0.990 0.922 0.967 0.988 0.998
CDKN1A 5 4 0.521 0.777 0.168 0.795 0.099 0.647 0.459 0.990 0.867 0.967 0.216 0.991
VDR binding sites 19 18 0.036 0.530 0.008 0.410 0.256 0.798
VDR binding sites e 19 18 0.036 0.511 0.530 0.999 0.008 0.227 0.410 0.990 0.256 0.747 0.798 0.991

aP of false discovery rate (BH; Benjamini–Hochberg or BH) method. b rs10485165 and rs10507577 (Bejamin et al. 2007) [27]. c rs1245541, rs4234798, rs700752, and rs780094. d Chromosome 8q24 region. e SNPs located in the VDR binding sites relating to colorectal cancer and Crohn’s disease risk as previously published (Ramagopalan et al. 2010) [19].