Table 5.
TCGA: Differentially DNA-methylated CpGs in IR significantly associated with primary invasive BC tissues, overall and stratified by BC molecular subtype
| Chr | CpG site§ | Position | Overall | ER/PR + | HER2/neu - | CpG Context | Gene | Gene region | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||||||
| chr2 | cg00765233* | 235,877,260 | 0.10 (0.01, 0.42) | 0.006 | 0.07 (0.003, 0.47) | 0.030 | 0.11 (0.01, 0.39) | 0.005 | OpenSea | SH3BP4 | 5'UTR |
| chr2 | cg14386946** | 179,315,284 | 2.65 (1.36, 6.11) | 0.010 | 5.40 (1.83, 26.55) | 0.011 | 2.68 (1.36, 6.24) | 0.010 | Island | PRKRA | Body |
| chr7 | cg01676795* | 75,586,348 | 2.98 (1.06, 9.43) | 0.046 | 5.18 (1.44, 43.15) | 0.026 | 2.97 (1.10, 9.82) | 0.039 | OpenSea | POR | Body |
| chr7 | cg24207108 | 98,600,653 | 1.14 (0.68, 1.73) | 0.567 | 2.26 (1.09, 5.11) | 0.034 | 1.12 (0.64, 1.77) | 0.653 | OpenSea | TRRAP | Body |
| chr8 | cg04684553 | 89,339,819 | 25.73 (3.46, 305.72) | 0.004 | NA | NA | 12.53 (2.68, 84.73) | 0.004 | N Shore | MMP16 | TSS200 |
| chr10 | cg26712428* | 105,218,771 | 0.45 (0.16, 1.22) | 0.119 | 0.06 (0.01, 0.37) | 0.006 | 0.47 (0.16, 1.22) | 0.116 | S Shore | CALHM1 | TSS200 |
| chr12 | cg20554753* | 16,940,870 | 0.25 (0.04, 1.12) | 0.085 | 0.04 (0.002, 0.32) | 0.007 | 0.26 (0.05, 1.12) | 0.086 | OpenSea | Intergenic | |
| chr12 | cg21565550 | 100,967,522 | 3.81 (1.48, 12.35) | 0.012 | 3.71 (1.23, 16.33) | 0.042 | 4.20 (1.58, 14.28) | 0.009 | Island | GAS2L3 | 5'UTR |
| chr17 | cg06892217** | 40,075,290 | 3.05 (1.44, 7.62) | 0.008 | 5.33 (1.96, 20.16) | 0.004 | 3.10 (1.45, 7.83) | 0.008 | Island | ACLY | TSS200 |
| chr17 | cg13274938 | 38,493,822 | 0.23 (0.05, 0.89) | 0.046 | 0.12 (0.02, 0.61) | 0.016 | 0.21 (0.04, 0.82) | 0.035 | N Shelf | RARA | Body |
| chr17 | cg18772573 | 71,257,980 | 0.77 (0.26, 2.01) | 0.617 | 0.11 (0.004, 0.74) | 0.044 | 0.77 (0.25, 2.04) | 0.626 | OpenSea | CPSF4L | 1stExon |
| chr19 | cg01969586 | 45,663,415 | 0.36 (0.09, 1.11) | 0.111 | 0.08 (0.01, 0.48) | 0.015 | 0.40 (0.09, 1.15) | 0.122 | OpenSea | NKPD1 | TSS200 |
| chr19 | cg15197202 | 10,488,965 | 0.66 (0.32, 1.28) | 0.227 | 0.35 (0.11, 0.90) | 0.047 | 0.67 (0.33, 1.30) | 0.244 | N Shelf | TYK2 | Body |
| chr19 | cg21066748 | 46,005,805 | 0.61 (0.21, 1.41) | 0.283 | 0.10 (0.01, 0.50) | 0.018 | 0.62 (0.22, 1.39) | 0.286 | N Shelf | Intergenic | |
| chr21 | cg06500161* | 43,656,587 | 3.80 (1.15, 15.47) | 0.043 | 1.01 (0.19, 5.51) | 0.993 | 3.86 (1.20, 15.78) | 0.034 | S Shore | ABCG1 | Body |
| chr21 | cg08309687£ | 35,320,596 | 0.30 (0.10, 0.87) | 0.031 | 0.28 (0.05, 1.30) | 0.131 | 0.30 (0.10, 0.88) | 0.033 | OpenSea | Intergenic | |
| chr21 | cg27243685* | 43,642,366 | 2.64 (1.39, 5.66) | 0.005 | 2.17 (0.63, 9.31) | 0.258 | 2.73 (1.37, 5.80) | 0.007 | S Shelf | ABCG1 | Body |
BC Breast cancer, Chr Chromosome, CI Confidence interval, CpG CpG dinucleotide; ER/PR + Estrogen receptor/progesterone receptor–positive, HER2/neu– Human epidermal growth factor receptor-2–negative, HR Hazard ratio, IR Insulin resistance, NA Not available, TCGA The Cancer Genomic Atlas, TSS200, 0–200 bp upstream of transcription start site, UTR Untranslated region. Numbers in bold face are statistically significant
§ Annotation used R v.0.6.0.IlluminaHumanMethylation450kanno.ilmn12.hg19: Annotation for Illumina's 450 k methylation arrays
aHR adjusted by age, tumor purity, and cell-type proportion (cancer epithelial cell types 1 to 5 and normal epithelial, stromal, and immune cells)
* Enhancer associated
** Promoter associated
£ Enhancer and promoter associated