Table 3.
Selecteda CpG-gene-cancer trios suggesting DNA methylation influencing cancer risk by regulating gene expression
| CpG | Chr | Pos (HG19) | Gene | Distance (Mb) | Cytoband | CpG-cancer | CpG-gene | Gene-cancer | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Dir | Pb | Dir | Pc | Dir | Pd | ||||||
| Breast cancer | |||||||||||
| cg23231268 | 3 | 46,792,462 | CCR9 | 0.848 | 3p21.31 | + | 1.43 × 10−8 | - | 1.15 × 10-4 | - | 7.36 × 10−8 |
| cg18035979 | 5 | 81,575,199 | ATP6AP1L | 0.000 | 5q14.2 | + | 1.21 × 10-9 | - | 3.05 × 10-5 | - | 1.95 × 10-9 |
| cg14587961 | 7 | 99,991,523 | PILRA | Body | 7q22.1 | + | 3.50 × 10−7 | + | 3.70 × 10-5 | + | 1.45 × 10-6 |
| cg07546779 | 8 | 29,495,175 | LEPROTL1 | -0.458 | 8p12 | - | 3.54 × 10-13 | - | 6.25 × 10-4 | + | 4.97 × 10-45 |
| cg02301815 | 17 | 44,249,491 | KANSL1-AS1 | -0.021 | 17q21.31 | + | 1.74 × 10−8 | - | 2.39 × 10-6 | - | 6.00 × 10−11 |
| Colorectal cancer | |||||||||||
| cg20019365 | 2 | 219,134,978 | RP11-378A13.1 | 0.013 | 2q35 | + | 5.06 × 10-13 | + | 7.41 × 10-5 | + | 4.27 × 10-19 |
| cg14130039 | 6 | 32,121,225 | HLA-DPA1 | -0.911 | 6p21.32 | - | 4.04 × 10−10 | - | 3.82 × 10-4 | + | 0.01 |
| cg12934461 | 15 | 90,792,652 | MAN2A2 | -0.653 | 15q26.1 | + | 9.66 × 10-9 | - | 6.27 × 10-4 | - | 5.05 × 10-130 |
| cg19877683 | 17 | 80,969,515 | FN3KRP | 0.281 | 17q25.3 | - | 7.53 × 10−8 | - | 1.87 × 10-5 | + | 8.10 × 10-25 |
| cg19133199 | 19 | 41,869,409 | B9D2 | Body | 19q13.2 | + | 2.48 × 10-15 | - | 3.14 × 10-5 | - | 3.08 × 10−10 |
| Renal cell cancer | |||||||||||
| cg13524857 | 11 | 69,240,192 | CCND1 | 0.216 | 11q13.3 | + | 1.61 × 10−7 | + | 3.61 × 10-3 | + | 6.11 × 10-62 |
| Lung cancer | |||||||||||
| cg09476067 | 6 | 30,418,581 | TRIM39 | 0.107 | 6p21.33 | - | 1.42 × 10-19 | + | 1.51 × 10-4 | - | 3.29 × 10-17 |
| cg15732223 | 11 | 118,551,206 | TREH | 0.001 | 11q23.3 | + | 3.46 × 10−8 | + | 5.44 × 10-4 | + | 3.18 × 10-6 |
| cg05651442 | 12 | 52,347,030 | KRT2 | -0.691 | 12q13.13 | + | 7.55 × 10−8 | - | 7.78 × 10-4 | - | 8.82 × 10−79 |
| cg22563815 | 15 | 78,856,949 | CHRNA3 | -0.028 | 15q25 | - | 1.02 × 10-26 | + | 4.08 × 10-5 | - | 3.91 × 10-35 |
| cg26812862 | 17 | 66,011,719 | HELZ | 0.770 | 17q24.3 | + | 1.20 × 10-9 | - | 1.18 × 10-3 | - | 6.89 × 10-27 |
| Ovarian cancer | |||||||||||
| cg18750960 | 2 | 177,016,417 | HOXD4 | Body | 2q31.1 | - | 8.85 × 10−11 | - | 3.74 × 10-3 | + | 8.65 × 10−8 |
| cg09087803 | 11 | 32,125,186 | QSER1 | -0.790 | 11p13 | + | 1.18 × 10−7 | - | 1.97 × 10-3 | - | 1.99 × 10-17 |
| cg17117718 | 17 | 43,663,208 | LRRC37A4P | 0.036 | 17q21.31 | + | 2.37 × 10−10 | - | 1.28 × 10-12 | - | 1.13 × 10-13 |
| Prostate cancer | |||||||||||
| cg24838316 | 6 | 29,895,260 | ZFP57 | 0.246 | 6p22.1 | - | 6.31 × 10−11 | + | 1.49 × 10-4 | - | 5.41 × 10-6 |
| cg16237302 | 11 | 47,429,196 | ARFGAP2 | 0.231 | 11p11.2 | + | 1.11 × 10−8 | - | 3.59 × 10-4 | - | 5.15 × 10-4 |
| cg00524169 | 19 | 39,138,063 | SAMD4B | -0.695 | 19q13.2 | - | 3.24 × 10-9 | + | 2.18 × 10-4 | - | 1.09 × 10-16 |
| cg15272956 | 20 | 62,332,704 | RTEL1 | 0.005 | 20q13.33 | + | 1.73 × 10-23 | + | 4.23 × 10-4 | + | 6.13 × 10-41 |
| cg05092891 | 21 | 37,535,885 | MORC3 | -0.170 | 21q22.12 | - | 3.65 × 10−8 | + | 5.70 × 10-6 | - | 1.34 × 10-31 |
| Testicular germ cell cancer | |||||||||||
| cg23581489 | 6 | 33,164,210 | B3GALT4 | -0.081 | 6p21.32 | + | 2.40 × 10-9 | - | 1.99 × 10-4 | - | 4.43 × 10-97 |
| cg22340370 | 7 | 2,019,882 | MRM2 | -0.254 | 7p22.3 | + | 2.21 × 10-16 | + | 1.07 × 10-3 | + | 5.29 × 10-6 |
| cg13353244 | 16 | 50,099,780 | BRD7 | -0.248 | 16q12.1 | - | 2.12 × 10−8 | + | 4.69 × 10-4 | - | 0.02 |
| cg04198914 | 17 | 36,106,025 | C17orf78 | 0.353 | 17q21.2 | - | 1.12 × 10-19 | + | 4.79 × 10-4 | - | 2.79 × 10−77 |
Chr chromosome, Mb mega base, Dir association direction.
a Selected from 854 CpG-gene-cancer trios demonstrating consistent directions of CpG-cancer, CpG-gene, and gene-cancer associations. In each trio, all of the three associations were statistically significant. Due to the large number of such trios, for each cancer, at most five trios in distinct loci are presented and all the other trois are available in Supplementary Data 21–27.
b P-values of associations between genetically predicted DNA methylation and cancer risk evaluated by applying GTEx-based DNA methylation prediction models to cancer GWAS data using SPrediXcan. Associations with Bonferroni-corrected P < 0.05 were considered significant.
c P-values of associations between tissue DNA methylation and gene expression calculated by linear regression using GTEx data. Associations with false discovery rate (FDR)-corrected P < 0.05 were considered significant.
d P-values of (1) associations between genetically predicted gene expression and cancer risk evaluated by applying GTEx-based gene expression prediction models to cancer GWAS data using SPrediXcan, or (2) differential gene expression between cancer and normal tissues obtained from GEPIA2. Associations or differential expressions with FDR-corrected P < 0.05 were considered significant. For genes with both P-values available, the one from SPrediXcan analysis is presented. All P-values from SPrediXcan analyses are highlighted in bold.