Introduction
Materials and methods
Study population
Tumor tissues and analysis of the ESR1A908G mutation
Risk factor information
Statistical methods
Results
Characteristics of cases and controls
Risk factors for breast cancer according to ESR1A908G mutation status
Risk factor | Controls (n= 790) | Mutation-positive cases (n= 37) | Mutation-negative cases (n= 616) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n
| (%) |
n
| (%) | OR1a
| 95% CI | OR2b
| 95% CI |
n
| (%) | OR1a
| 95% CI | OR2b
| 95% CI | |
Age (years)
| ||||||||||||||
50+ | 383 | (48.5) | 19 | (51.4) |
c
|
c
| 246 | (39.9) |
c
|
c
| ||||
<50 | 407 | (51.5) | 18 | (48.6) | 370 | (60.1) | ||||||||
Race
| ||||||||||||||
White | 458 | (58.0) | 25 | (67.6) |
c
|
c
| 371 | (60.2) |
c
|
c
| ||||
African-American | 332 | (42.0) | 12 | (32.4) | 245 | (39.8) | ||||||||
Menopausal status
| ||||||||||||||
Postmenopausal | 435 | (55.1) | 22 | (59.5) | 1.00 | --- | 1.00d
| --- | 295 | (47.9) | 1.00 | --- | 1.00d
| --- |
Premenopausal | 355 | (44.9) | 15 | (40.5) | 1.27 | 0.40–4.05 | 1.63 | 0.47–5.64 | 321 | (52.1) | 1.08 | 0.78–1.50 | 1.12 | 0.80–1.58 |
First-degree family history of BC
| ||||||||||||||
No | 671 | (88.3) | 26 | (72.2) | 1.00 | --- | 1.00e
| --- | 523 | (87.0) | 1.00 | --- | 1.00e
| --- |
Yes | 89 | (11.7) | 10 | (27.8) | 2.54 | 1.16–5.55 | 2.69 | 1.15–6.28 | 78 | (13.0) | 1.17 | 0.84–1.62 | 1.22 | 0.87–1.71 |
First-degree family history of BC and/or ovarian cancer
| ||||||||||||||
No | 664 | (87.4) | 24 | (66.7) | 1.00 | --- | 1.00e
| --- | 514 | (85.5) | 1.00 | --- | 1.00e
| --- |
Yes | 96 | (12.6) | 12 | (33.3) | 3.13 | 1.49–6.58 | 3.48 | 1.56–7.76 | 87 | (14.5) | 1.21 | 0.88–1.66 | 1.27 | 0.92–1.76 |
Prior benign breast biopsy
| ||||||||||||||
No | 649 | (82.4) | 28 | (80.0) | 1.00 | --- | 1.00 | --- | 518 | (84.2) | 1.00 | --- | 1.00 | --- |
Yes | 139 | (17.6) | 7 | (20.0) | 1.21 | 0.51–2.87 | 1.17 | 0.47–2.91 | 97 | (15.8) | 1.00 | 0.75–1.33 | 0.94 | 0.70–1.28 |
BMI
| ||||||||||||||
<25 | 250 | (32.2) | 15 | (41.7) | 1.00 | --- | 1.00f
| --- | 224 | (37.1) | 1.00 | --- | 1.00f
| --- |
25 to <30 | 250 | (32.2) | 10 | (27.8) | 0.73 | 0.32–1.69 | 0.78 | 0.32–1.90 | 180 | (29.8) | 0.87 | 0.66–1.14 | 0.83 | 0.63–1.10 |
30+ | 277 | (35.6) | 11 | (30.5) | 0.80 | 0.34–1.89 | 0.76 | 0.29–1.98 | 200 | (33.1) | 0.85 | 0.64–1.12 | 0.80 | 0.60–1.08 |
Smoking
| ||||||||||||||
Never | 423 | (53.5) | 18 | (48.7) | 1.00 | --- | 1.00g
| --- | 322 | (52.3) | 1.00 | --- | 1.00g
| --- |
Ever | 367 | (46.5) | 19 | (51.3) | 1.16 | 0.59–2.27 | 1.04 | 0.49–2.19 | 294 | (47.7) | 1.08 | 0.87–1.34 | 1.11 | 0.88–1.41 |
Alcohol consumption
| ||||||||||||||
Never | 231 | (29.3) | 14 | (37.8) | 1.00 | --- | 1.00h
| --- | 178 | (28.9) | 1.00 | --- | 1.00h
| --- |
Ever | 558 | (70.7) | 23 | (62.2) | 0.79 | 0.39–1.63 | 0.74 | 0.32–1.71 | 438 | (71.1) | 0.95 | 0.75–1.22 | 0.88 | 0.67–1.16 |
Age at menarche (years)
| ||||||||||||||
14+ | 203 | (25.8) | 10 | (27.0) | 1.00 | --- | 1.00i
| --- | 130 | (21.1) | 1.00 | --- | 1.00i
| --- |
13 | 206 | (26.2) | 9 | (24.3) | 0.96 | 0.38–2.44 | 1.22 | 0.43–3.41 | 165 | (26.8) | 1.28 | 0.95–1.75 | 1.38 | 1.01–1.91 |
≤12 | 378 | (48.0) | 18 | (48.6) | 1.12 | 0.50–2.50 | 1.42 | 0.57–3.53 | 321 | (52.1) | 1.36 | 1.04–1.79 | 1.46 | 1.09–1.94 |
Parity
| ||||||||||||||
Nulliparous | 89 | (11.3) | 5 | (13.5) | 1.00 | --- | 1.00j
| --- | 100 | (16.2) | 1.00 | --- | 1.00j
| --- |
Parous | 701 | (88.7) | 32 | (86.5) | 0.93 | 0.34–2.54 | 1.30 | 0.44–3.85 | 516 | (83.8) | 0.76 | 0.55–1.04 | 0.92 | 0.65–1.29 |
Age at first full-term pregnancy (years)
| ||||||||||||||
Nulliparous | 89 | (11.3) | 5 | (13.9) | 1.00 | --- | 1.00j
| --- | 100 | (16.3) | 1.00 | --- | 1.00j
| --- |
10–19 | 236 | (29.9) | 8 | (22.2) | 0.74 | 0.23–2.39 | 1.03 | 0.28–3.79 | 181 | (29.5) | 0.82 | 0.57–1.16 | 0.99 | 0.67–1.46 |
20–24 | 265 | (33.6) | 11 | (30.5) | 0.82 | 0.27–2.52 | 1.14 | 0.35–3.74 | 181 | (29.5) | 0.73 | 0.51–1.03 | 0.88 | 0.60–1.27 |
25+ | 198 | (25.2) | 12 | (33.3) | 1.20 | 0.40–3.63 | 1.71 | 0.51–5.78 | 152 | (24.8) | 0.73 | 0.51–1.05 | 0.90 | 0.60–1.34 |
Number full-term births
| ||||||||||||||
Nulliparous | 89 | (11.3) | 5 | (13.5) | 1.00 | --- | 1.00j
| --- | 100 | (16.2) | 1.00 | --- | 1.00j
| --- |
1 | 141 | (17.8) | 5 | (13.5) | 0.74 | 0.20–2.69 | 0.99 | 0.26–3.78 | 117 | (19.0) | 0.79 | 0.54–1.17 | 0.89 | 0.59–1.34 |
2 or more | 560 | (70.9) | 27 | (73.0) | 0.98 | 0.36–2.72 | 1.43 | 0.47–4.35 | 399 | (64.8) | 0.75 | 0.54–1.03 | 0.92 | 0.65–1.31 |
Breastfeeding
| ||||||||||||||
Never | 476 | (60.3) | 26 | (70.3) | 1.00 | --- | 1.00k
| --- | 413 | (67.0) | 1.00 | --- | 1.00k
| --- |
Ever | 314 | (39.7) | 11 | (29.7) | 0.52 | 0.25–1.09 | 0.29 | 0.12–0.71 | 203 | (33.0) | 0.70 | 0.56–0.87 | 0.69 | 0.53–0.89 |
Age at menopause (years) (postmenopausal)
| ||||||||||||||
<45 | 192 | (45.6) | 10 | (45.5) | 1.00 | - | 1.00d
| --- | 117 | (39.9) | 1.00 | --- | 1.00d
| --- |
45–49 | 119 | (28.3) | 7 | (31.8) | 1.13 | 0.42–3.08 | 1.47 | 0.45–4.79 | 93 | (31.7) | 1.38 | 0.96–1.97 | 1.39 | 0.95–2.03 |
50+ | 110 | (26.1) | 5 | (22.7) | 0.82 | 0.27–2.53 | 1.32 | 0.36–4.77 | 83 | (28.3) | 1.39 | 0.95–2.03 | 1.50 | 1.00–2.24 |
Duration of ovarian function (years) (postmenopausal)
| ||||||||||||||
≤29 | 139 | (33.2) | 6 | (27.2) | 1.00 | --- | 1.00d
| --- | 79 | (27.0) | 1.00 | --- | 1.00d
| --- |
30–35 | 141 | (33.6) | 10 | (45.4) | 1.66 | 0.58–4.74 | 1.78 | 0.49–6.46 | 98 | (33.4) | 1.33 | 0.90–1.95 | 1.32 | 0.88–1.99 |
36+ | 139 | (33.2) | 6 | (27.2) | 0.98 | 0.30–3.18 | 1.38 | 0.35–5.45 | 116 | (39.6) | 1.69 | 1.15–2.48 | 1.82 | 1.21–2.74 |
Ptrend
| 0.97 | 0.70 | 0.007 | 0.004 |
Risk factor | Controls (n= 790) | Mutation-positive cases (n= 37) | Mutation-positive cases vs. controls | Mutation-negative cases (n= 616) | Mutation-negative cases vs. controls | Mutation-positive vs. mutation-negative cases | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
n
| (%) |
n
| (%) | ORa
| 95% CI |
n
| (%) | ORa
| 95% CI | ORa
| 95% CI | |
OC use
| ||||||||||||
Never | 319 | (40.4) | 14 | (37.8) | 1.00 | --- | 224 | (36.5) | 1.00 | --- | 1.00 | --- |
Ever | 470 | (59.6) | 23 | (62.2) | 1.72 | 0.66–4.44 | 390 | (63.5) | 1.15 | 0.87–1.52 | 1.53 | 0.61–3.84 |
OC duration
| ||||||||||||
Never | 319 | (40.4) | 14 | (37.8) | 1.00 | --- | 224 | (36.5) | 1.00 | --- | 1.00 | --- |
<5 years | 232 | (29.4) | 8 | (21.6) | 1.08 | 0.35–3.38 | 194 | (31.6) | 1.27 | 0.94–1.73 | 1.01 | 0.33–3.06 |
5–10 years | 162 | (20.5) | 8 | (21.6) | 1.75 | 0.53–5.77 | 123 | (20.0) | 0.95 | 0.67–1.35 | 1.79 | 0.59–5.43 |
>10 years | 76 | (9.6) | 7 | (8.9) | 3.73 | 1.16–12.03 | 73 | (11.9) | 1.18 | 0.77–1.81 | 2.66 | 0.81–8.67 |
Ptrend
| 0.02 | 0.84 | 0.07 | |||||||||
Age at first use of OCs
| ||||||||||||
Never | 319 | (40.4) | 14 | (37.8) | 1.00 | --- | 224 | (36.6) | 1.00 | --- | 1.00 | --- |
≤20 years | 215 | (27.2) | 8 | (21.6) | 1.18 | 0.32–4.42 | 192 | (31.4) | 0.99 | 0.69–1.41 | 1.44 | 0.41–5.09 |
>20 years | 255 | (32.3) | 15 | (40.5) | 1.81 | 0.71–4.63 | 196 | (32.0) | 1.20 | 0.89–1.60 | 1.56 | 0.61–3.96 |
Age at last use of OCs
| ||||||||||||
Never | 319 | (40.4) | 14 | (37.8) | 1.00 | --- | 224 | (36.6) | 1.00 | --- | 1.00 | --- |
≤30 years | 273 | (34.6) | 10 | (27.0) | 1.18 | 0.36–3.90 | 226 | (36.9) | 1.10 | 0.80–1.52 | 1.39 | 0.45–4.25 |
>30 years | 197 | (25.0) | 13 | (35.1) | 1.97 | 0.75–5.15 | 162 | (26.5) | 1.16 | 0.85–1.58 | 1.63 | 0.62–4.29 |
Year of first OC use
| ||||||||||||
Never | 319 | (40.4) | 14 | (37.8) | 1.00 | --- | 224 | (36.6) | 1.00 | --- | 1.00 | --- |
≤1975 | 389 | (49.3) | 19 | (51.4) | 1.72 | 0.67–4.43 | 292 | (47.7) | 1.15 | 0.87–1.52 | 1.54 | 0.61–3.89 |
>1975 | 81 | (10.3) | 4 | (10.8) | 1.51 | 0.28–8.12 | 96 | (15.7) | 0.98 | 0.62–1.55 | 1.58 | 0.35–7.13 |
First use before first full-term pregnancy
| ||||||||||||
No | 233 | (54.8) | 11 | (57.9) | 1.00 | --- | 169 | (51.1) | 1.00 | --- | 1.00 | --- |
Yes | 192 | (45.2) | 8 | (42.1) | 0.66 | 0.15–2.93 | 162 | (48.9) | 1.12 | 0.76–1.66 | 0.78 | 0.18–3.31 |
Recency of OC use (years since stopping)
| ||||||||||||
Never | 319 | (42.3) | 14 | (37.8) | 1.00 | --- | 224 | (39.4) | 1.00 | --- | 1.00 | --- |
10+ | 374 | (49.5) | 17 | (45.9) | 1.70 | 0.65–4.43 | 278 | (48.8) | 1.15 | 0.86–1.52 | 1.52 | 0.59–3.92 |
<10 | 62 | (8.2) | 6 | (16.2) | 3.63 | 0.80–16.45 | 67 | (11.8) | 1.06 | 0.65–1.72 | 3.65 | 0.86–15.47 |
Ptrend
| 0.10 | 0.56 | 0.10 | |||||||||
OC duration and recency of use (years since stopping)
| ||||||||||||
Never | 319 | (42.3) | 14 | (37.8) | 1.00 | --- | 224 | (39.4) | 1.00 | --- | 1.00 | --- |
<10, <10 | 31 | (4.1) | 2 | (5.4) | 1.43 | 0.19–10.77 | 32 | (5.6) | 0.84 | 0.44–1.58 | 3.04 | 0.46–20.06 |
<10, 10+ | 315 | (41.7) | 13 | (35.1) | 1.53 | 0.55–4.26 | 245 | (43.1) | 1.21 | 0.90–1.62 | 1.25 | 0.46–3.41 |
10+, <10 | 31 | (4.1 | 4 | (10.8) | 6.49 | 1.32–31.89 | 35 | (6.2) | 1.32 | 0.73–2.38 | 3.53 | 0.73–17.09 |
10+, 10+ | 59 | (7.8) | 4 | (10.8) | 1.93 | 0.52–7.11 | 33 | (5.8) | 0.81 | 0.49–1.35 | 3.01 | 0.78–11.59 |
Postmenopausal HRT use
| ||||||||||||
Never | 219 | (50.3) | 13 | (59.1) | 1.00 | --- | 180 | (61.0) | 1.00 | --- | 1.00 | --- |
Ever | 216 | (49.7) | 9 | (40.9) | 0.83 | 0.28–2.42 | 115 | (39.0) | 0.62 | 0.44–0.87 | 1.23 | 0.42–3.61 |
Postmenopausal HRT duration
| ||||||||||||
Never | 219 | (50.3) | 13 | (59.1) | 1.00 | --- | 180 | (61.0) | 1.00 | --- | 1.00 | --- |
<5 years | 105 | (24.1) | 3 | (13.6) | 0.60 | 0.14–2.51 | 56 | (19.0) | 0.61 | 0.40–0.92 | 1.37 | 0.30–6.24 |
5+ years | 111 | (25.6) | 6 | (27.3) | 1.07 | 0.31–3.70 | 59 | (20.0) | 0.64 | 0.42–0.96 | 1.17 | 0.35–3.91 |