Table 4.
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].