Table 2.
Genotype and allele frequencies of rs832583 (MAP3K1), rs16865677 (SF3B1), rs3819122 (SMAD4), and rs12456284 (SMAD4) in BRCA1/2-negative breast cancer cases and controls.
| Genotype or Allele |
Controls (%) (n = 1285) |
All BC Cases (n = 492) | Families with ≥2 BC and/or OC Cases (n = 316) |
Families with a Single Case, Diagnosis at ≤50 Years of Age (n = 176) |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| BC Cases (%) |
OR [95% CI] |
p-Value a | BC Cases (%) |
OR [95% CI] |
p-Value a | BC Cases (%) |
OR [95% CI] |
p-Value a | ||
| rs832583 (MAP3K1) | ||||||||||
| C/C | 473 (36.8) | 198 (40.3) | 1.0 (ref) | - | 140 (44.3) | 1.0 (ref) | - | 59 (33.3) | 1.0 (ref) | - |
| C/A | 587 (45.7) | 219 (44.5) | 0.8 [0.6–1.0] | 0.32 | 132 (41.7) | 0.7 [0.5–0.9] | 0.04 | 86 (49.2) | 1.1 [0.8–1.5] | 0.42 |
| A/A | 225 (17.4) | 75 (15.2) | 0.7 [0.5–1.0] | 0.14 | 44 (14.0) | 0.6 [0.4–0.9] | 0.03 | 31 (17.5) | 1.1 [0.7–1.7] | 0.72 |
| C/A+A/A | 812 (63.2) | 294 (59.7) | 0.8 [0.6–1.0] | 0.18 | 176 (55.7) | 0.7 [0.5–0.9] | 0.01 | 117 (66.7) | 1.1 [0.8–1.6] | 0.40 |
| Allele C | 1533 (59.6) | 615 (62.5) | 1.0 (ref) | - | 412 (65.2) | 1.0 (ref) | - | 204 (57.9) | 1.0 (ref) | - |
| Allele A | 1037 (40.4) | 369 (37.5) | 0.8 [0.7–1.0] | 0.14 | 220 (34.8) | 0.7 [0.6–0.9] | 0.01 | 148 (42.1) | 1.0 [0.8–1.3] | 0.56 |
| rs16865677 (SF3B1) | ||||||||||
| G/G | 870 (67.7) | 319 (64.9) | 1.0 (ref) | - | 216 (68.5) | 1.0 (ref) | - | 103 (58.5) | 1.0 (ref) | - |
| G/T | 364 (28.3) | 151 (30.6) | 1.1 [0.8–1.4] | 0.31 | 89 (27.9) | 0.9 [0.7–1.2] | 0.88 | 62 (35.2) | 1.4 [1.0–2.0] | 0.03 |
| T/T | 51 (4.0) | 22 (4.5) | 1.1 [0.7–2.0] | 0.49 | 11 (3.6) | 0.8 [0.4–1.6] | 0.86 | 11 (6.3) | 1.8 [0.9–3.5] | 0.09 |
| G/T+T/T | 415 (32.3) | 173 (35.1) | 1.1 [0.9–1.4] | 0.25 | 100 (31.5) | 0.9 [0.7–1.2] | 0.83 | 73 (41.5) | 1.4 [1.0–2.0] | 0.01 |
| Allele G | 2104 (81.9) | 789 (80.1) | 1.0 (ref) | - | 521 (82.5) | 1.0 (ref) | - | 268 (76.1) | 1.0 (ref) | - |
| Allele T | 466 (18.1) | 195 (19.9) | 1.1 [0.9–1.4] | 0.11 | 111 (17.5) | 0.9 [0.7–1.2] | 0.76 | 84 (23.9) | 1.4 [1.0–1.8] | 0.01 |
| rs3819122 (SMAD4) | ||||||||||
| A/A | 519 (40.4) | 143 (29.1) | 1.0 (ref) | - | 91 (28.8) | 1.0 (ref) | - | 52 (29.8) | 1.0 (ref) | - |
| A/C | 576 (44.8) | 269 (54.5) | 1.6 [1.3–2.1] | <0.0001 | 166 (52.4) | 1.6 [1.2–2.1] | 0.0005 | 103 (58.4) | 1.7 [1.2–2.5] | 0.001 |
| C/C | 190 (14.8) | 80 (16.3) | 1.5 [1.1–2.1] | 0.01 | 59 (18.8) | 1.7 [1.2–2.5] | 0.002 | 21 (11.8) | 1.1 [0.6–1.8] | 0.77 |
| A/C+C/C | 766 (59.6) | 349 (70.9) | 1.6 [1.3–2.0] | <0.0001 | 225 (71.2) | 1.6 [1.2–2.1] | 0.0001 | 124 (70.2) | 1.6 [1.1–2.2] | 0.006 |
| Allele A | 1614 (62.8) | 555 (56.4) | 1.0 (ref) | - | 348 (55.0) | 1.0 (ref) | - | 207 (59.0) | 1.0 (ref) | - |
| Allele C | 956 (37.2) | 429 (43.6) | 1.3 [1.1–1.5] | 0.0005 | 284 (45.0) | 1.3 [1.1–1.6] | 0.0005 | 145 (41.0) | 1.1 [0.9–1.4] | 0.20 |
| rs12456284 (SMAD4) | ||||||||||
| A/A | 685 (53.3) | 227 (46.2) | 1.0 (ref) | - | 148 (46.9) | 1.0 (ref) | - | 79 (45.1) | 1.0 (ref) | - |
| A/G | 427 (33.2) | 196 (39.9) | 1.3 [1.0–1.7] | 0.005 | 122 (38.7) | 1.3 [1.0–1.7] | 0.04 | 74 (41.8) | 1.5 [1.0–2.1] | 0.02 |
| G/G | 173 (13.5) | 69 (13.9) | 1.2 [0.8–1.6] | 0.24 | 46 (14.4) | 1.2 [0.8–1.7] | 0.28 | 23 (13.1) | 1.1 [0.7–1.8] | 0.60 |
| A/G+G/G | 600 (46.7) | 265 (53.8) | 1.3 [1.0–1.6] | 0.008 | 168 (53.1) | 1.2 [1.0–1.6] | 0.04 | 97 (54.9) | 1.4 [1.0–1.9] | 0.03 |
| Allele A | 1797 (69.9) | 650 (66.1) | 1.0 (ref) | - | 418 (66.1) | 1.0 (ref) | - | 232 (66.0) | 1.0 (ref) | - |
| Allele G | 773 (30.1) | 334 (33.9) | 1.2 [1.0–1.3] | 0.03 | 214 (33.9) | 1.1 [0.9–1.4] | 0.07 | 120 (34.0) | 1.2 [0.9–1.5] | 0.14 |
BC: breast cancer, OC: ovarian cancer, OR: odds ratio, CI: confidence interval; a Fisher’s exact test; bold values are statistically significant (p < 0.05).