Background
Methods
Datasets
DNAm age calculation
Statistics
Results
Relationship between chronological age and DNAm age
Characteristics and the relationships with DNAm age in breast cancer tissues
Characteristics | Total | DNAm age (quartile)b | P value a | |||
---|---|---|---|---|---|---|
First | Second | Third | Fourth | |||
Age (years) | ||||||
< 40 | 96 (8.9) | 52 (19.3) | 20 (7.4) | 13 (4.8) | 11 (4.1) |
< 0.01
|
40–60 | 496 (46.1) | 145 (53.9) | 148 (55.0) | 115 (42.8) | 88 (32.7) | |
> 60 | 484 (45.0) | 72 (26.8) | 101 (37.5) | 141 (52.4) | 170 (63.2) | |
Race | ||||||
African American | 178 (16.5) | 72 (26.8) | 40 (14.9) | 35 (13.0) | 31 (11.5) |
< 0.01
|
White or other | 898 (83.5) | 197 (73.2) | 229 (85.1) | 234 (87.0) | 238 (88.5) | |
Menopausal status | ||||||
Premenopausal | 229 (21.3) | 80 (29.7) | 57 (21.2) | 54 (20.1) | 38 (14.1) |
< 0.01
|
Post-menopausal | 736 (68.4) | 153 (56.9) | 185 (68.8) | 187 (69.5) | 211 (78.4) | |
Unknown | 111 (10.3) | 36 (13.4) | 27 (10.0) | 28 (10.4) | 20 (7.4) | |
ER | ||||||
Negative | 178 (16.6) | 99 (36.8) | 53 (19.7) | 20 (7.4) | 6 (2.2) |
< 0.01
|
Positive | 588 (54.6) | 95 (35.3) | 140 (52.0) | 161 (59.9) | 192 (71.4) | |
Unknown | 310 (28.8) | 75 (27.9) | 76 (28.3) | 88 (32.7) | 71 (26.4) | |
PR | ||||||
Negative | 251 (23.3) | 122 (45.4) | 67 (24.9) | 36 (13.4) | 26 (9.7) |
< 0.01
|
Positive | 512 (47.6) | 70 (26.0) | 126 (46.8) | 145 (53.9) | 171 (63.6) | |
Unknown | 313 (29.1) | 77 (28.6) | 76 (28.3) | 88 (32.7) | 72 (26.7) | |
HER2 | ||||||
Negative | 644 (59.9) | 156 (58.0) | 162 (60.2) | 155 (57.6) | 171 (63.5) | 0.33 |
Equivocal/positive | 118 (11.0) | 37 (13.7) | 31 (11.5) | 24 (9.0) | 26 (9.7) | |
Unknown | 314 (29.1) | 76 (28.3) | 76 (28.3) | 90 (33.4) | 72 (26.8) | |
PAM50 | ||||||
Luminal A | 229 (21.3) | 25 (9.3) | 51 (19.0) | 71 (26.4) | 82 (30.5) |
< 0.01
|
Luminal B | 122 (11.3) | 22 (8.2) | 25 (9.3) | 28 (10.4) | 47 (17.5) | |
HER2-enriched & Basal-like | 155 (14.4) | 84 (31.2) | 41 (15.2) | 22 (8.2) | 8 (3.0) | |
Unknown | 570 (53.0) | 138 (51.3) | 152 (56.5) | 148 (55.0) | 132 (49.0) | |
Clinical stage | ||||||
I/II | 568 (52.8) | 136 (50.6) | 149 (55.4) | 136 (50.6) | 147 (54.6) | 0.26 |
III/IV | 187 (17.4) | 56 (20.8) | 38 (14.1) | 44 (16.3) | 49 (18.2) | |
Unknown | 321 (29.8) | 77 (28.6) | 82 (30.5) | 89 (33.1) | 73 (27.1) |
Associations between DNAm age and prognosis
DNAm Age | N | Overall survival | Five-year survival | ||||
---|---|---|---|---|---|---|---|
HR (95% CI) a | HR (95% CI) b | HR (95% CI) c | HR (95% CI) a | HR (95% CI) b | HR (95% CI) c | ||
Continuous | |||||||
(Per ten year) | 1076 | 1.01 (0.94–1.08) | 0.92 (0.85–1.00) | 0.94 (0.86–1.02) | 0.92 (0.84–1.01) |
0.84 (0.75–0.93)
|
0.85 (0.76–0.96)
|
Categorical (quartile) d | |||||||
First | 269 | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) |
Second | 269 | 0.80 (0.51–1.26) | 0.66 (0.42–1.05) | 0.64 (0.39–1.04) | 0.59 (0.34–1.03) |
0.49 (0.28–0.85)
|
0.52 (0.29–0.92)
|
Third | 269 | 0.79 (0.51–1.24) |
0.56 (0.35–0.89)
|
0.56 (0.34–0.93)
| 0.66 (0.39–1.12) |
0.46 (0.27–0.78)
|
0.49 (0.27–0.87)
|
Fourth | 269 | 1.00 (0.66–1.53) |
0.56 (0.35–0.90)
| 0.60 (0.36–1.04) | 0.60 (0.34–1.03) |
0.33 (0.18–0.59)
|
0.38 (0.20–0.72)
|
P for trend | 0.939 |
0.014
| 0.065 | 0.075 |
0.001
|
0.004
| |
Categorical (First quartile and second-fourth quartile) | |||||||
First | 269 | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) |
Second-Fourth | 807 | 0.86 (0.61–1.22) |
0.59 (0.41–0.86)
|
0.60 (0.40–0.91)
|
0.61 (0.41–0.93)
|
0.42 (0.27–0.65)
|
0.47 (0.29–0.76)
|
DNAm Age | N | Overall recurrence free survival | Five-year recurrence free survival | ||||
---|---|---|---|---|---|---|---|
HR (95% CI) a | HR (95% CI) b | HR (95% CI) c | HR (95% CI) a | HR (95% CI) b | HR (95% CI) c | ||
Continuous | |||||||
(Per ten year) | 889 |
0.89 (0.81–0.98)
|
0.86 (0.77–0.96)
|
0.86 (0.76–0.97)
|
0.87 (0.78–0.98)
|
0.84 (0.75–0.95)
|
0.86 (0.75–0.98)
|
Categorical (quartile) d | |||||||
First | 215 | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) |
Second | 230 | 0.82 (0.48–1.39) | 0.76 (0.44–1.31) | 0.77 (0.43–1.36) | 0.77 (0.43–1.36) | 0.70 (0.39–1.25) | 0.71 (0.39–1.31) |
Third | 227 | 0.82 (0.49–1.37) | 0.72 (0.42–1.23) | 0.70 (0.39–1.29) | 0.76 (0.43–1.36) | 0.65 (0.36–1.17) | 0.68 (0.36–1.32) |
Fourth | 217 |
0.48 (0.25–0.90)
|
0.40 (0.21–0.78)
|
0.39 (0.19–0.80)
|
0.39 (0.19–0.80)
|
0.31 (0.15–0.66)
|
0.32 (0.14–0.74)
|
P for trend |
0.031
|
0.009
|
0.014
|
0.014
|
0.003
|
0.020
| |
Categorical (First quartile and second-fourth quartile) | |||||||
First | 215 | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) | 1.00 (Ref) |
Second-Fourth | 674 | 0.71 (0.46–1.08) |
0.64 (0.41–1.00)
| 0.66 (0.39–1.09) | 0.64 (0.40–1.02) |
0.57 (0.35–0.93)
| 0.62 (0.35–1.07) |
Stratified variables | DNAm age (quartile)a | Survival | Recurrence | ||
---|---|---|---|---|---|
N | HRb (95% CI) | N | HRb (95% CI) | ||
Menopause Status | |||||
Pre | First | 80 | 1.00 (ref) | 72 | 1.00 (ref) |
Second-Fourth | 149 | 0.87 (0.30–2.58) | 133 | 1.16 (0.42–3.21) | |
Post | First | 153 | 1.00 (ref) | 117 | 1.00 (ref) |
Second-Fourth | 583 |
0.40 (0.24–0.69)
| 486 | 0.58 (0.29–1.16) | |
P for interaction | 0.3761 | 0.963 | |||
Clinical stage | |||||
Stage I&II | First | 136 | 1.00 (ref) | 103 | 1.00 (ref) |
Second-Fourth | 432 | 1.24 (0.62–2.49) | 341 | 0.80 (0.32–1.96) | |
Stage III&IV | First | 56 | 1.00 (ref) | 39 | 1.00 (ref) |
Second-Fourth | 131 |
0.39 (0.17–0.91)
| 97 | 1.07 (0.39–2.92) | |
P for interaction | 0.159 | 0.665 | |||
ER status | |||||
negative | First | 99 | 1.00 (ref) | 77 | 1.00 (ref) |
Second-Fourth | 79 | 0.82 (0.31–2.15) | 61 | 0.60 (0.19–1.84) | |
positive | First | 95 | 1.00 (ref) | 67 | 1.00 (ref) |
Second-Fourth | 493 |
0.54 (0.29–0.99)
| 385 | 0.77 (0.33–1.78) | |
P for interaction | 0.092 | 0.9972 | |||
HER2 status | |||||
negative | First | 156 | 1.00 (ref) | 119 | 1.00 (ref) |
Second-Fourth | 488 | 0.92 (0.51–1.64) | 382 | 1.14 (0.57–2.31) | |
Equivocal /positive | First | 37 | 1.00 (ref) | 25 | 1.00 (ref) |
Second-Fourth | 81 | 0.37 (0.09–1.58) | 63 | 0.18 (0.03–1.21) | |
P for interaction | 0.217 | 0.133 | |||
PAM50 | |||||
Luminal A | First | 25 | 1.00 (ref) | 13 | 1.00 (ref) |
Second-Fourth | 204 | 0.72 (0.17–2.97) | 149 | 0.59 (0.11–3.24) | |
Luminal B | First | 22 | 1.00 (ref) | 16 | 1.00 (ref) |
Second-Fourth | 100 | 0.65 (0.21–2.06) | 73 | 0.29 (0.06–1.46) | |
HER2-enriched&Basal-like | First | 84 | 1.00 (ref) | 61 | 1.00 (ref) |
Second-Fourth | 71 | 1.91 (0.67–5.41) | 48 | 0.66 (0.17–2.53) | |
P for interaction |
0.016
| 0.966 |