Table 4.
WHI: Differentially DNA-methylated CpGs in IR significantly associated with an invasive BC risk, overall and stratified by BC molecular subtype
| Chr | CpG site§ | Position | Crude | DM and BMI adjusted | DM, BMI, and WHR adjusted | CpG context | Gene | Gene region | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | ||||||
| Overall | |||||||||||
| chr1 | cg05399785 | 3,564,031 | 1.43 (1.05, 1.94) | 0.022 | 1.42 (1.04, 1.93) | 0.027 | 1.43 (1.05, 1.95) | 0.023 | N Shelf | WDR8 | Body |
| chr1 | cg11832534 | 3,563,998 | 1.35 (1.03, 1.76) | 0.030 | 1.34 (1.02, 1.76) | 0.035 | 1.35 (1.03, 1.78) | 0.030 | N Shelf | WDR8 | Body |
| chr1 | cg16395997 | 3,562,798 | 1.49 (1.05, 2.10) | 0.026 | 1.49 (1.04, 2.11) | 0.028 | 1.50 (1.05, 2.13) | 0.024 | S Shore | WDR8 | Body |
| chr1 | cg16246545 | 120,255,941 | 0.76 (0.60, 0.96) | 0.021 | 0.77 (0.61, 0.97) | 0.028 | 0.76 (0.60, 0.97) | 0.025 | S Shore | PHGDH | Body |
| chr6 | cg01254034 | 28,543,667 | 0.80 (0.66, 0.98) | 0.033 | 0.79 (0.64, 0.97) | 0.023 | 0.79 (0.64, 0.96) | 0.021 | OpenSea | SCAND3 | Body |
| chr16 | cg05807722 | 67,697,020 | 0.81 (0.65, 1.00) | 0.054 | 0.80 (0.65, 1.00) | 0.048 | 0.81 (0.65, 1.00) | 0.049 | S Shore | C16orf48 | 3'UTR |
| chr17 | cg24366564* | 2,843,149 | 1.39 (1.07, 1.80) | 0.015 | 1.37 (1.05, 1.79) | 0.019 | 1.38 (1.06, 1.80) | 0.018 | OpenSea | RAP1GAP2 | Body |
| ER/PR + | |||||||||||
| chr1 | cg05399785 | 3,564,031 | 1.62 (1.16, 2.24) | 0.004 | 1.61 (1.15, 2.23) | 0.005 | 1.62 (1.16, 2.26) | 0.004 | N Shelf | WDR8 | Body |
| chr1 | cg11832534 | 3,563,998 | 1.48 (1.11, 1.98) | 0.008 | 1.47 (1.10, 1.98) | 0.010 | 1.49 (1.10, 2.00) | 0.009 | N Shelf | WDR8 | Body |
| chr1 | cg16395997 | 3,562,798 | 1.61 (1.11, 2.34) | 0.013 | 1.61 (1.10, 2.35) | 0.014 | 1.62 (1.11, 2.37) | 0.013 | S Shore | WDR8 | Body |
| chr1 | cg20671910 | 151,262,619 | 1.35 (1.03, 1.78) | 0.031 | 1.35 (1.02, 1.78) | 0.033 | 1.37 (1.04, 1.80) | 0.027 | OpenSea | ZNF687 | Body |
| chr7 | cg01676795* | 75,586,348 | 1.72 (1.13, 2.63) | 0.012 | 1.72 (1.12, 2.64) | 0.013 | 1.75 (1.14, 2.69) | 0.011 | OpenSea | POR | Body |
| chr10 | cg00541500 | 45,642,600 | 1.33 (1.01, 1.74) | 0.042 | 1.32 (1.00, 1.73) | 0.047 | 1.32 (1.01, 1.74) | 0.044 | OpenSea | LOC100133308 | Body |
| chr10 | cg01391548* | 97,068,696 | 1.31 (1.00, 1.71) | 0.049 | 1.36 (1.04, 1.78) | 0.026 | 1.36 (1.04, 1.79) | 0.026 | OpenSea | Intergenic | |
| chr17 | cg24366564* | 2,843,149 | 1.55 (1.17, 2.06) | 0.003 | 1.53 (1.15, 2.05) | 0.004 | 1.54 (1.16, 2.06) | 0.003 | OpenSea | RAP1GAP2 | Body |
| HER2/neu - | |||||||||||
| chr1 | cg05399785 | 3,564,031 | 1.52 (1.06, 2.18) | 0.022 | 1.49 (1.03, 2.14) | 0.033 | 1.49 (1.03, 2.15) | 0.032 | N Shelf | WDR8 | Body |
| chr1 | cg11832534 | 3,563,998 | 1.47 (1.07, 2.02) | 0.018 | 1.44 (1.04, 1.99) | 0.028 | 1.44 (1.04, 2.00) | 0.027 | N Shelf | WDR8 | Body |
| chr1 | cg16395997 | 3,562,798 | 1.60 (1.06, 2.42) | 0.026 | 1.57 (1.03, 2.40) | 0.037 | 1.57 (1.03, 2.41) | 0.036 | S Shore | WDR8 | Body |
| chr1 | cg16246545 | 120,255,941 | 0.75 (0.57, 1.00) | 0.048 | 0.77 (0.58, 1.02) | 0.067 | 0.76 (0.57, 1.02) | 0.065 | S Shore | PHGDH | Body |
| chr8 | cg20907614* | 29,914,963 | 0.63 (0.42, 0.95) | 0.028 | 0.66 (0.43, 1.01) | 0.053 | 0.66 (0.43, 1.01) | 0.054 | OpenSea | Intergenic | |
| chr10 | cg00541500 | 45,642,600 | 1.38 (1.02, 1.87) | 0.035 | 1.36 (1.01, 1.85) | 0.044 | 1.37 (1.01, 1.85) | 0.042 | OpenSea | LOC100133308 | Body |
| chr10 | cg08284263* | 92,958,627 | 1.32 (0.96, 1.82) | 0.090 | 1.39 (1.00, 1.92) | 0.047 | 1.38 (1.00, 1.91) | 0.050 | OpenSea | Intergenic | |
| chr11 | cg17058475 | 68,607,737 | 0.61 (0.42, 0.90) | 0.013 | 0.65 (0.44, 0.97) | 0.033 | 0.65 (0.44, 0.96) | 0.030 | N Shore | CPT1A | 5'UTR |
| chr17 | cg24366564* | 2,843,149 | 1.66 (1.21, 2.28) | 0.002 | 1.64 (1.19, 2.25) | 0.003 | 1.64 (1.19, 2.27) | 0.002 | OpenSea | RAP1GAP2 | Body |
BC Breast cancer, BMI Body mass index, Chr Chromosome, CI Confidence interval, CpG CpG dinucleotide, DM ever been treated for diabetes mellitus; ER/PR + Estrogen receptor/progesterone receptor–positive, HER2/neu– Human epidermal growth factor receptor-2–negative, HR Hazard ratio, IR Insulin resistance, UTR Untranslated region, WHI Women’s Health Initiative, WHR Waist-to-hip ratio
§ Annotation used R v.0.6.0.IlluminaHumanMethylation450kanno.ilmn12.hg19: Annotation for Illumina's 450 k methylation arrays
a HR adjusted by age and leukocyte heterogeneities (CD8+CD28−CD45RA− T cell, naïve CD8 T cell, plasma blast, CD4+ T cell, natural killer cell, monocyte, and granulocyte)
* Enhancer associated