Clinical and demographic characteristics of carriers with rare missense variants
| Variable |
PALB2 carriers (n=35) |
BRCA1 carriers (n=31) |
BRCA2 carriers (n=85) | Non-carriers* (n=7372) | P value† | P value‡ | P value§ |
| Age at diagnosis (mean±SD) | 51.9±10.6 | 47.5±10.8 | 51.7±11.7 | 52.5±10.7 | 0.748 | 0.009 | 0.460 |
| Age distribution (years) | 0.705 | 0.086 | 0.273 | ||||
| <30 | 0 (0.0) | 0 (0.0) | 2 (2.4) | 99 (1.4) | |||
| 30–39 | 5 (14.7) | 7 (23.3) | 9 (10.6) | 651 (8.9) | |||
| 40–49 | 9 (26.5) | 11 (36.7) | 29 (34.1) | 2211 (30.2) | |||
| 50–59 | 10 (29.4) | 9 (30.0) | 20 (23.5) | 2499 (34.1) | |||
| >60 | 10 (29.4) | 3 (10.0) | 25 (29.4) | 1869 (25.5) | |||
| Ethnicity | 0.807 | 0.002 | 0.003 | ||||
| Chinese | 27 (77.1) | 17 (54.8) | 55 (64.7) | 5597 (76) | |||
| Malay | 4 (11.4) | 13 (41.9) | 11 (12.9) | 1060 (14.4) | |||
| Indian | 4 (11.4) | 1 (3.2) | 17 (20.0) | 629 (8.5) | |||
| Other | 0 (0.0) | 0 (0.0) | 2 (2.4) | 77 (1.0) | |||
| Family history of breast cancer, first deg | 0.467 | 0.797 | 0.351 | ||||
| Yes | 3 (8.8) | 5 (16.1) | 15 (17.9) | 1048 (14.4) | |||
| No | 31 (91.2) | 26 (83.9) | 69 (82.1) | 6218 (85.6) | |||
| Family history of ovarian cancer, first deg | 1.000 | 0.079 | 0.638 | ||||
| Yes | 0 (0.0) | 2 (7.1) | 0 (0.0) | 106 (1.6) | |||
| No | 28 (100.0) | 26 (92.9) | 77 (100.0) | 6332 (98.4) | |||
| Bilaterality | 1.000 | 1.000 | 1.000 | ||||
| Yes | 1 (2.9) | 1 (3.2) | 3 (3.6) | 301 (4.1) | |||
| No | 34 (97.1) | 30 (96.8) | 80 (96.4) | 7025 (95.9) | |||
| Tumour stage | 0.684 | 0.450 | 0.569 | ||||
| Stage 0 | 2 (7.1) | 0 (0) | 4 (5.7) | 692 (11.4) | |||
| Stage I | 11 (39.3) | 8 (36.4) | 23 (32.9) | 1923 (31.6) | |||
| Stage II | 12 (42.9) | 10 (45.5) | 28 (40.0) | 2288 (37.5) | |||
| Stage III | 2 (7.1) | 3 (13.6) | 11 (15.7) | 950 (15.6) | |||
| Stage IV | 1 (3.6) | 1 (4.5) | 4 (5.7) | 242 (4.0) | |||
| Tumour grade | 0.855 | 0.010 | 0.252 | ||||
| Low | 5 (16.1) | 3 (11.5) | 5 (7.8) | 937 (14.9) | |||
| Intermediate | 15 (48.4) | 5 (19.2) | 29 (45.3) | 2798 (44.4) | |||
| High | 11 (35.5) | 18 (69.2) | 30 (46.9) | 2564 (40.7) | |||
| ER status | 1.000 | 0.168 | 1.000 | ||||
| Positive | 23 (74.2) | 14 (58.3) | 57 (72.2) | 4739 (72.3) | |||
| Negative | 8 (25.8) | 10 (41.7) | 22 (27.8) | 1814 (27.7) | |||
| PR status | 0.575 | 0.829 | 0.546 | ||||
| Positive | 18 (58.1) | 14 (60.9) | 45 (60.0) | 4040 (63.7) | |||
| Negative | 13 (41.9) | 9 (39.1) | 30 (40.0) | 2298 (36.3) | |||
| HER2 status | 0.229 | 0.610 | 0.424 | ||||
| Positive | 12 (41.4) | 4 (22.2) | 17 (25.4) | 1662 (30.8) | |||
| Negative | 17 (58.6) | 14 (77.8) | 50 (74.6) | 3739 (69.2) | |||
| Triple negative breast cancer | 1.000 | 0.017 | 0.053 | ||||
| Yes | 3 (8.6) | 7 (22.6) | 13 (15.3) | 654 (8.9) | |||
| No | 32 (91.4) | 24 (77.4) | 72 (84.7) | 6716 (91.1) | |||
| Study | 0.712 | 0.093 | 0.463 | ||||
| MyBrCa | 14 (40.0) | 18 (58.1) | 40 (47.1) | 3177 (43.1) | |||
| SGBCC | 21 (60.0) | 13 (41.9) | 45 (52.9) | 4195 (56.9) | |||
*Non-carriers: Do not carry either protein-truncating or rare missense variants (with AGVGD scores of C15 and above) in three genes.
†PALB2 mutation carriers versus non-carriers.
‡BRCA1 mutation carriers versus non-carriers.
§BRCA2 mutation carriers versus non-carriers.
MyBrCa, Malaysian Breast Cancer Genetic Study; PALB2, partner and localiser of BRCA2; SGBCC, Singapore Breast Cancer Cohort Study.