Table 3

Clinical and demographic characteristics of carriers with rare missense variants

VariablePALB2 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±10.647.5±10.851.7±11.752.5±10.70.7480.0090.460
Age distribution (years)0.7050.0860.273
 <300 (0.0)0 (0.0)2 (2.4)99 (1.4)
 30–395 (14.7)7 (23.3)9 (10.6)651 (8.9)
 40–499 (26.5)11 (36.7)29 (34.1)2211 (30.2)
 50–5910 (29.4)9 (30.0)20 (23.5)2499 (34.1)
 >6010 (29.4)3 (10.0)25 (29.4)1869 (25.5)
Ethnicity0.8070.0020.003
 Chinese27 (77.1)17 (54.8)55 (64.7)5597 (76)
 Malay4 (11.4)13 (41.9)11 (12.9)1060 (14.4)
 Indian4 (11.4)1 (3.2)17 (20.0)629 (8.5)
 Other0 (0.0)0 (0.0)2 (2.4)77 (1.0)
Family history of breast cancer, first deg0.4670.7970.351
 Yes3 (8.8)5 (16.1)15 (17.9)1048 (14.4)
 No31 (91.2)26 (83.9)69 (82.1)6218 (85.6)
Family history of ovarian cancer, first deg1.0000.0790.638
 Yes0 (0.0)2 (7.1)0 (0.0)106 (1.6)
 No28 (100.0)26 (92.9)77 (100.0)6332 (98.4)
Bilaterality1.0001.0001.000
 Yes1 (2.9)1 (3.2)3 (3.6)301 (4.1)
 No34 (97.1)30 (96.8)80 (96.4)7025 (95.9)
Tumour stage0.6840.4500.569
 Stage 02 (7.1)0 (0)4 (5.7)692 (11.4)
 Stage I11 (39.3)8 (36.4)23 (32.9)1923 (31.6)
 Stage II12 (42.9)10 (45.5)28 (40.0)2288 (37.5)
 Stage III2 (7.1)3 (13.6)11 (15.7)950 (15.6)
 Stage IV1 (3.6)1 (4.5)4 (5.7)242 (4.0)
Tumour grade0.8550.0100.252
 Low5 (16.1)3 (11.5)5 (7.8)937 (14.9)
 Intermediate15 (48.4)5 (19.2)29 (45.3)2798 (44.4)
 High11 (35.5)18 (69.2)30 (46.9)2564 (40.7)
ER status1.0000.1681.000
 Positive23 (74.2)14 (58.3)57 (72.2)4739 (72.3)
 Negative8 (25.8)10 (41.7)22 (27.8)1814 (27.7)
PR status0.5750.8290.546
 Positive18 (58.1)14 (60.9)45 (60.0)4040 (63.7)
 Negative13 (41.9)9 (39.1)30 (40.0)2298 (36.3)
HER2 status0.2290.6100.424
 Positive12 (41.4)4 (22.2)17 (25.4)1662 (30.8)
 Negative17 (58.6)14 (77.8)50 (74.6)3739 (69.2)
Triple negative breast cancer1.0000.0170.053
 Yes3 (8.6)7 (22.6)13 (15.3)654 (8.9)
 No32 (91.4)24 (77.4)72 (84.7)6716 (91.1)
Study0.7120.0930.463
 MyBrCa14 (40.0)18 (58.1)40 (47.1)3177 (43.1)
 SGBCC21 (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.