Table 1.
Summary statistics of cancer distribution among relatives, stratified by index women’s genetic predisposition status
| Genetic predisposition | Index women |
Female relatives |
All relatives |
||||
|---|---|---|---|---|---|---|---|
| No. | Breast cancer patients, No. (%) | No. | Breast cancer patients, No. (%) | No. | Hereditary breast and ovarian cancer syndrome–related cancer patients, No. (%) | Any cancer patients, No. (%) | |
| Protein-truncating variants | |||||||
| All | 13 226 | 7677 (58.0) | 31 754 | 2094 (6.6)d | 63 376 | 4942 (7.8) | 12 013 (19.0) |
| Noncarriersa | 12 744 | 7295 (57.2) | 30 618 | 1962 (6.4) | 61 132 | 4685 (7.7) | 11 517 (18.8) |
| Any risk geneb | 482 | 382 (79.3) | 1140 | 133 (11.7)d | 2253 | 259 (11.5) | 501 (22.2) |
| CHEK2 | 219 | 160 (73.1) | 530 | 53 (10.0) | 1040 | 101 (9.7) | 209 (20.1) |
| BRCA2 | 82 | 72 (87.8) | 189 | 21 (11.1) | 370 | 44 (11.9) | 85 (23.0) |
| ATM | 63 | 51 (81.0) | 149 | 14 (9.4) | 302 | 28 (9.3) | 64 (21.2) |
| BRCA1 | 59 | 56 (94.9) | 132 | 29 (22.0) | 256 | 46 (18.0) | 68 (26.6) |
| PALB2 | 25 | 20 (80.0) | 55 | 8 (14.5) | 113 | 17 (15.0) | 33 (29.2) |
| BARD1 | 20 | 14 (70.0) | 57 | 7 (12.3) | 102 | 11 (10.8) | 22 (21.6) |
| RAD51C | 20 | 16 (80.0) | 45 | 6 (13.3) | 99 | 18 (18.2) | 27 (27.3) |
| RAD51D | 2 | 1 (50.0) | 3 | 0 (0.0) | 8 | 0 (0.0) | 2 (20.0) |
| Polygenic risk scorec | |||||||
| All | 28 362 | 7221 (25.5) | 66 288 | 3897 (5.9)d | 133 389 | 9812 (7.4) | 24 018 (18.0) |
| 0%-25% | 6073 | 750 (12.3) | 14 398 | 571 (4.0) | 28 978 | 1837 (6.3) | 4914 (17.0) |
| 25%-50% | 6594 | 1289 (19.5) | 15 662 | 803 (5.1) | 31 554 | 2165 (6.9) | 5653 (17.9) |
| 50%-75% | 7216 | 1937 (26.8) | 16 941 | 1048 (6.2) | 34 188 | 2600 (7.6) | 6205 (18.1) |
| 75%-100% | 8474 | 3241 (38.2) | 19 902 | 1528 (7.7)d | 39 910 | 3336 (8.4) | 7544 (18.9) |
a
Noncarrier status was defined as the absence of protein-truncating variants in any studied risk gene, including CHEK2, BRCA2, ATM, BRCA1, PALB2, BARD1, RAD51C, and RAD51D.
b
Carrier status of any studied risk gene.
c
Polygenic risk score quartiles were defined according to breast cancer–free index women at study entry.
d
Of breast cancer patients in female relatives, 6.3% (133 of 2094) were linked to protein-truncating variant carriers of any of the studied risk genes, and 39.2% (1528 of 3897) were linked to index women in the top polygenic risk score quartile.