Introduction
Materials and methods
Subjects
Genotyping
Statistical analysis
Results
Characteristic |
BRCA1
|
BRCA2
| ||
---|---|---|---|---|
Unaffected | Breast cancer | Unaffected | Breast cancer | |
Number | 6,209 | 6,390 | 3,322 | 3,810 |
Person-years follow-up | 264,903 | 263,068 | 147,053 | 168,201 |
Median age at censure (IQR1) | 42 (34 to 50) | 40 (34 to 47) | 43 (34 to 53) | 43 (37 to 50) |
Age at censure, N (%) | ||||
< 30 | 1,189 (19.2) | 691 (10.8) | 611 (18.4) | 306 (8.0) |
30 to 39 | 1,161 (26.8) | 2,445 (38.3) | 834 (25.1) | 1,141 (30.0) |
40 to 49 | 1,765 (28.4) | 2,191 (34.3) | 865 (26.0) | 1,394 (36.6) |
50 to 59 | 1,058 (17.0) | 812 (12.7) | 566 (17.0) | 687 (18.0) |
60 to 69 | 380 (6.1) | 198 (3.1) | 302 (9.1) | 226 (5.9) |
70+ | 156 (2.5) | 53 (0.8) | 144 (4.3) | 56 (1.5) |
Year of birth, N (%) | ||||
< 1920 | 28 (0.5) | 30 (0.5) | 23 (0.7) | 44 (1.2) |
1920 to 1929 | 131 (2.1) | 196 (3.1) | 99 (3.0) | 167 (4.4) |
1930 to 1939 | 369 (5.9) | 516 (8.1) | 232 (7.0) | 430 (11.3) |
1940 to 1949 | 832 (13.4) | 1,341 (21.0) | 458 (13.8) | 896 (23.5) |
1950 to 1959 | 1,409 (22.7) | 1,989 (31.1) | 691 (20.8) | 1,160 (30.5) |
1960 to 1969 | 1,703 (27.4) | 1,666 (26.1) | 902 (27.2) | 868 (22.8) |
1970+ | 1,737 (28.0) | 652 (10.2) | 917 (27.6) | 245 (6.4) |
Mutation Class, N (%) | ||||
Class 12 | 4,063 (65.4) | 3,878 (60.7) | 3,114 (93.7) | 3,520 (92.4) |
Class 22 | 1,780 (28.7) | 1,973 (30.9) | 72 (2.2) | 100 (2.6) |
Other | 366 (5.9) | 539 (8.4) | 136 (4.1) | 190 (5.0) |
Associations with cancer risk for BRCA1 mutation carriers
Mutation | Genotype | Unaffected N (%) | Affecteda N (%) | HR | 95% CI | P-value |
---|---|---|---|---|---|---|
CDK2NA/B - rs1011970 | ||||||
BRCA1
| GG | 4,318 (69.7) | 4,460 (70.0) | 1 | ||
GT | 1,698 (27.4) | 1,719 (27.0) | 1.01 | 0.94 to 1.09 | ||
TT | 180 (2.9) | 195 (3.1) | 1.11 | 0.91 to 1.35 | ||
2-df test | 0.61 | |||||
per allele | 1.03 | 0.96 to 1.09 | 0.45 | |||
BRCA2
| GG | 2,279 (68.7) | 2,586 (67.9) | 1 | ||
GT | 943 (28.4) | 1,098 (28.9) | 1.08 | 0.98 to 1.19 | ||
TT | 94 (2.8) | 123 (3.2) | 1.23 | 0.95 to 1.59 | ||
2-df test | 0.12 | |||||
per allele |
1.09
|
1.00 to 1.18
|
0.048
| |||
ZNF365 - rs10995190
| ||||||
BRCA1
| GG | 4,394 (70.9) | 4,556 (71.5) | 1 | ||
GA | 1,656 (26.7) | 1,662 (26.1) | 0.98 | 0.91 to 1.06 | ||
AA | 147 (2.4) | 156 (2.5) | 0.98 | 0.79 to 1.20 | ||
2-df test | 0.89 | |||||
per allele | 0.99 | 0.93 to 1.05 | 0.64 | |||
BRCA2
| GG | 2,334 (70.4) | 2,802 (73.7) | 1 | ||
GA | 913 (27.5) | 923 (24.3) |
0.86
|
0.78 to 0.96
| ||
AA | 68 (20.1) | 79 (2.1) | 0.96 | 0.69 to 1.34 | ||
2-df test |
0.019
| |||||
per allele |
0.90
|
0.82 to 0.98
|
0.015
| |||
ZMIZ1 - rs704010
| ||||||
BRCA1
| CC | 2,476 (40.3) | 2,504 (39.8) | 1 | ||
CT | 2,814 (45.8) | 2,894 (46.0) | 1.03 | 0.96 to 1.10 | ||
TT | 855 (13.9) | 888 (14.1) | 1.04 | 0.93 to 1.15 | ||
2-df test | 0.69 | |||||
per allele | 1.02 | 0.97 to 1.07 | 0.42 | |||
BRCA2
| CC | 1,286 (39.3) | 1,443 (38.4) | 1 | ||
CT | 1,496 (45.7) | 1,779 (47.3) | 1.07 | 0.97 to 1.18 | ||
TT | 494 (15.8) | 539 (14.3) | 0.99 | 0.86 to 1.14 | ||
2-df test | 0.32 | |||||
per allele | 1.01 | 0.95 to 1.08 | 0.73 | |||
10p15 - rs2380205
| ||||||
BRCA1
| CC | 1,609 (32.5) | 1,710 (32.1) | 1 | ||
CT | 2,410 (48.7) | 2,625 (49.3) | 1.01 | 0.93 to 1.09 | ||
TT | 933 (18.8) | 990 (18.6) | 1.02 | 0.92 to 1.13 | ||
2-df test | 0.95 | |||||
per allele | 1.01 | 0.96 to 1.06 | 0.75 | |||
BRCA2
| CC | 1,013 (32.8) | 1,163 (31.8) | 1 | ||
CT | 1,516 (49.1) | 1,816 (49.7) | 1.05 | 0.95 to 1.16 | ||
TT | 560 (18.1) | 681 (18.6) | 1.03 | 0.90 to 1.17 | ||
2-df test | 0.63 | |||||
per allele | 1.02 | 0.96 to 1.09 | 0.57 | |||
11q13 - rs614367
| ||||||
BRCA1
| CC | 4,516 (73.2) | 4,581 (72.1) | 1 | ||
CT | 1,511 (24.5) | 1,618 (25.5) | 1.05 | 0.98 to 1.14 | ||
TT | 146 (2.4) | 154 (2.4) | 1.07 | 0.87 to 1.32 | ||
2-df test | 0.34 | |||||
per allele | 1.05 | 0.98 to 1.12 | 0.15 | |||
BRCA2
| CC | 2,432 (73.6) | 2,723 (71.8) | 1 | ||
CT | 799 (24.1) | 983 (26.0) | 1.06 | 0.96 to 1.17 | ||
TT | 76 (2.3) | 83 (2.2) | 0.97 | 0.72 to 1.30 | ||
2-df test | 0.54 | |||||
per allele | 1.03 | 0.95 to 1.12 | 0.46 | |||
12q24 - rs1292011
| ||||||
BRCA1
| AA | 1,292 (34.3) | 1,331 (35.4) | 1 | ||
AG | 1,825 (48.4) | 1,775 (47.3) | 0.98 | 0.89 to 1.07 | ||
GG | 653 (17.3) | 649 (17.3) | 1.01 | 0.90 to 1.14 | ||
2-df test | 0.80 | |||||
per allele | 1.00 | 0.94 to 1.06 | 0.99 | |||
BRCA2
| AA | 824 (35.2) | 908 (35.9) | 1 | ||
AG | 1,095 (46.7) | 1,225 (48.4) | 1.03 | 0.92 to 1.16 | ||
GG | 423 (18.1) | 397 (15.7) |
0.84
|
0.72 to 0.99
| ||
2-df test |
0.03
| |||||
per allele | 0.94 | 0.87 to 1.01 | 0.10 | |||
PTHLH - rs10771399
| ||||||
BRCA1
| AA | 4,913 (79.4) | 5,221 (82.0) |
1
| ||
AG | 1,194 (19.3) | 1,082 (17.0) |
0.87
|
0.80 to 0.95
| ||
GG | 83 (1.3) | 65 (1.0) |
0.77
|
0.57 to 1.04
| ||
2-df test |
1.5 × 10
-3
| |||||
per allele |
0.87
|
0.81 to 0.94
|
3.2 × 10
-4
| |||
BRCA2
| AA | 2,649 (80.0) | 3,085 (81.2) | 1 | ||
AG | 620 (18.7) | 679 (17.9) | 0.95 | 0.85 to 1.07 | ||
GG | 45 (1.4) | 34 (0.9) | 0.74 | 0.47 to 1.15 | ||
2-df test | 0.31 | |||||
per allele | 0.93 | 0.84 to 1.04 | 0.20 | |||
9q31.2 - rs865686
| ||||||
BRCA1
| TT | 2,521 (40.1) | 2,640 (41.4) | 1 | ||
TG | 2,872 (46.4) | 2,849 (44.7) | 0.95 | 0.88 to 1.01 | ||
GG | 799 (12.9) | 880 (13.8) | 1.05 | 0.95 to 1.17 | ||
2-df test | 0.06 | |||||
per allele | 1 | 0.96 to 1.05 | 0.85 | |||
BRCA2
| TT | 1,277 (38.6) | 1,581 (41.6) | 1 | ||
TG | 1,610 (48.6) | 1,717 (45.2) |
0.86
|
0.78 to 0.95
| ||
GG | 425 (12.8) | 501 (13.2) | 0.96 | 0.84 to 1.11 | ||
2-df test |
7.3 × 10
-3
| |||||
per allele | 0.95 | 0.89 to 1.01 | 0.10 |
Unaffected, N | Affected, N | HR | 95% CI | P-value | |
---|---|---|---|---|---|
Excluding prevalent breast cancer cases | |||||
CDK2NA/B -rs1011970
| |||||
BRCA1
| 6,200 | 3,152 | 1.05 | 0.98 to 1.14 | 0.18 |
BRCA2
| 3,319 | 1,950 | 1.10 | 1.00 to 1.22 | 0.05 |
ZNF365 - rs10995190
| |||||
BRCA1
| 6,201 | 3,151 | 0.96 | 0.89 to 1.04 | 0.34 |
BRCA2
| 3,318 | 1,949 | 0.90 | 0.81 to 1.00 | 0.05 |
ZMIZ1 - rs704010
| |||||
BRCA1
| 6,149 | 3,094 | 1.02 | 0.96 to 1.08 | 0.53 |
BRCA2
| 3,276 | 1,919 | 0.98 | 0.91 to 1.06 | 0.64 |
10p15 - rs2380205
| |||||
BRCA1
| 4,955 | 2,764 | 1.02 | 0.95 to 1.08 | 0.64 |
BRCA2
| 3,092 | 1,884 | 1.00 | 0.93 to 1.08 | 0.92 |
11q13 - rs614367
| |||||
BRCA1
| 6,177 | 3,144 | 1.01 | 0.94 to 1.10 | 0.73 |
BRCA2
| 3,310 | 1,944 | 0.99 | 0.89 to 1.10 | 0.88 |
12q24 - rs1292011
| |||||
BRCA1
| 3,773 | 1,798 | 1.04 | 0.97 to 1.12 | 0.29 |
BRCA2
| 2,345 | 1,220 | 0.96 | 0.88 to 1.06 | 0.41 |
PTHLH - rs10771399
| |||||
BRCA1
| 6,194 | 3,152 | 0.85 | 0.77 to 0.93 | 5.8 × 10-4 |
BRCA2
| 3,317 | 1,944 | 0.89 | 0.78 to 1.00 | 0.06 |
9q31.2 - rs865686
| |||||
BRCA1
| 6,196 | 3,149 | 1.01 | 0.95 to 1.07 | 0.72 |
BRCA2
| 3,315 | 1,946 | 0.94 | 0.87 to 1.02 | 0.15 |
BRCA1
analysis by mutation class
| |||||
CDK2NA/B -rs1011970
| |||||
Class1 | 4,040 | 3,843 | 1.01 | 0.94 to 1.10 | 0.72 |
Class2 | 1,771 | 1,958 | 1.03 | 0.91 to 1.16 | 0.66 |
ZNF365 - rs10995190
| |||||
Class1 | 4,058 | 3,844 | .99 | 0.92 to 1.07 | 0.80 |
Class2 | 1,774 | 1,957 | 0.97 | 0.86 to 1.09 | 0.59 |
ZMIZ1 - rs704010
| |||||
Class1 | 3,998 | 3,787 | 1.04 | 0.98 to 1.10 | 0.22 |
Class2 | 1,767 | 1,936 | 1.01 | 0.92 to 1.11 | 0.85 |
10p15 - rs2380205
| |||||
Class1 | 3,664 | 3,538 | 1.01 | 0.95 to 1.07 | 0.82 |
Class2 | 931 | 1,263 | 1.03 | 0.91 to 1.15 | 0.67 |
11q13 - rs614367
| |||||
Class1 | 4,024 | 3,833 | 1.10 | 1.02 to 1.19 | 0.02 |
Class2 | 1,764 | 1,948 | 0.94 | 0.84 to 1.06 | 0.32 |
12q24 - rs1292011
| |||||
Class1 | 2,812 | 2,521 | 0.99 | 0.92 to 1.06 | 0.71 |
Class2 | 642 | 797 | 0.97 | 0.84 to 1.12 | 0.68 |
PTHLH - rs10771399
| |||||
Class1 | 4,035 | 3,841 | 0.82 | 0.74 to 0.90 | 3.1 × 10-5 |
Class2 | 1,770 | 1,953 | 1.00 | 0.87 to 1.15 | 0.99 |
9q31.2 - rs865686
| |||||
Class1 | 4,038 | 3,840 | 0.98 | 0.92 to 1.04 | 0.48 |
Class2 | 1,769 | 1,957 | 1.03 | 0.94 to 1.14 | 0.49 |
Breast cancer | Ovarian cancer | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Unaffected N (%) | Breast cancer N (%) | Ovarian cancer N (%) | HR | 95% CI | P-value | HR | 95% CI | P-value | ||
CDK2NA/B - rs1011970
| ||||||||||
BRCA1
| GG | 3,328 (69.6) | 4,424 (69.9) | 1,026 (70.1) | 1 | 1 | ||||
GT | 1,309 (27.4) | 1,710 (27.0) | 398 (27.2) | 1.03 | 0.95 to 1.11 | 1.10 | 0.95 to 1.26 | |||
TT | 142 (3.0) | 194 (3.1) | 39 (2.7) | 1.09 | 0.88 to 1.35 | 0.90 | 0.61 to 1.32 | |||
2-df test | 0.57 | 0.35 | ||||||||
per allele | 1.04 | 0.91 to 1.11 | 0.30 | 1.04 | 0.93 to 1.17 | 0.48 | ||||
BRCA2
| GG | 1,972 (68.6) | 2578 (67.9) | 315 (69.5) | 1 | 1 | ||||
GT | 815 (28.4) | 1097 (28.9) | 129 (28.5) | 1.09 | 0.98 to 1.21 | 1.07 | 0.85 to 1.35 | |||
TT | 86 (3.0) | 122 (3.2) | 9 (2.0) | 1.19 | 0.91 to 1.57 | 0.84 | 0.40 to 1.77 | |||
2-df test | 0.15 | 0.74 | ||||||||
per allele |
1.09
|
1.00 to 1.19
|
0.05
| 1.03 | 0.84 to 1.25 | 0.81 | ||||
ZNF365 - rs10995190
| ||||||||||
BRCA1
| GG | 3,408 (71.3) | 4,523 (71.5) | 1,019 (69.6) | 1 | 1 | ||||
GA | 1,258 (26.3) | 1,650 (26.1) | 410 (28.0) | 1.00 | 0.93 to 1.08 | 1.12 | 0.98 to 1.28 | |||
AA | 113 (2.4) | 155 (2.5) | 35 (2.4) | 0.96 | 0.78 to 1.20 | 0.90 | 0.61 to 1.33 | |||
2-df test | 0.94 | 0.23 | ||||||||
per allele | 0.99 | 0.93 to 1.06 | 0.88 | 1.06 | 0.95 to 1.19 | 0.32 | ||||
BRCA2
| GG | 2,033 (70.4) | 2,795 (73.7) | 318 (70.2) | 1 | 1 | ||||
GA | 794 (27.7) | 920 (24.3) | 122 (26.9) |
0.86
|
0.78 to 0.96
| 0.99 | 0.78 to 1.25 | |||
AA | 55 (1.9) | 79 (2.1) | 13 (2.9) | 1.03 | 0.74 to 1.43 | 1.58 | 0.83 to 3.03 | |||
2-df test |
0.02
| 0.37 | ||||||||
per allele |
0.90
|
0.82 to 0.99
|
0.03
| 1.06 | 0.87 to 1.31 | 0.55 | ||||
ZMIZ1 - rs704010
| ||||||||||
BRCA1
| CC | 1,904 (40.2) | 2,493 (40.0) | 583 (40.1) | 1 | 1 | ||||
CT | 2,172 (45.9) | 2,871 (46.0) | 665 (45.7) | 1.02 | 0.95 to 1.10 | 1.01 | 0.89 to 1.15 | |||
TT | 660 (13.9) | 877 (14.1) | 206 (14.2) | 1.02 | 0.92 to 1.14 | 1.01 | 0.84 to 1.22 | |||
2-df test | 0.67 | 0.99 | ||||||||
per allele | 1.01 | 0.97 to 1.07 | 0.58 | 1.01 | 0.92 to 1.10 | 0.90 | ||||
BRCA2
| CC | 1,109 (39.0) | 1,439 (38.4) | 181 (40.1) | 1 | 1 | ||||
CT | 1,306 (46.0) | 1,774 (47.3) | 192 (43.4) | 1.06 | 0.96 to 1.17 | 0.96 | 0.76 to 1.20 | |||
TT | 426 (15.0) | 538 (14.3) | 69 (15.6) | 1.00 | 0.86 to 1.15 | 1.05 | 0.77 to 1.43 | |||
2-df test | 0.46 | 0.81 | ||||||||
per allele | 1.01 | 0.95 to 1.08 | 0.72 | 1.01 | 0.87 to 1.18 | 0.90 | ||||
10p15 - rs2380205
| ||||||||||
BRCA1
| CC | 1,183 (32.2) | 1,698 (32.1) | 438 (33.2) | 1 | 1 | ||||
CT | 1,796 (48.9) | 2,605 (49.3) | 634 (48.1) | 0.99 | 0.91 to 1.08 | 0.91 | 0.79 to 1.05 | |||
TT | 696 (18.9) | 981 (18.6) | 246 (18.7) | 1.00 | 0.90 to 1.12 | 0.94 | 0.78 to 1.14 | |||
2-df test | 0.96 | 0.45 | ||||||||
per allele | 1.00 | 0.95 to 1.06 | 0.98 | 0.96 | 0.87 to 1.06 | 0.40 | ||||
BRCA2
| CC | 872 (32.6) | 1,161 (31.8) | 143 (33.7) | 1 | 1 | ||||
CT | 1,321 (49.4) | 1,812 (49.6) | 199 (46.9) | 1.04 | 0.94 to 1.16 | 0.94 | 0.74 to 1.19 | |||
TT | 481 (18.0) | 678 (18.6) | 82 (19.3) | 1.03 | 0.90 to 1.18 | 1.01 | 0.75 to 1.38 | |||
2-df test | 0.74 | 0.82 | ||||||||
per allele | 1.02 | 0.95 to 1.09 | 0.61 | 1.00 | 0.85 to 1.16 | 0.98 | ||||
11q13 - rs614367
| ||||||||||
BRCA1
| CC | 3,439 (72.3) | 4,547 (72.1) | 1,111 (76.2) | 1 | 1 | ||||
CT | 1,212 (25.5) | 1,606 (25.5) | 311 (21.3) | 1.02 | 0.94 to 1.11 |
0.83
|
0.72 to 0.96
| |||
TT | 109 (2.3) | 154 (2.4) | 37 (2.5) | 1.12 | 0.91 to 1.39 | 1.20 | 0.81 to 1.76 | |||
2-df test | 0.52 |
0.03
| ||||||||
per allele | 1.03 | 0.91 to 1.10 | 0.35 | 0.91 | 0.80 to 1.03 | 0.13 | ||||
BRCA2
| CC | 2,106 (73.5) | 2,716 (71.9) | 333 (73.8) | 1 | 1 | ||||
CT | 693 (24.2) | 981 (26.0) | 108 (24.0) | 1.05 | 0.95 to 1.16 | 0.95 | 0.74 to 1.21 | |||
TT | 66 (2.3) | 83 (2.2) | 10 (2.2) | 0.96 | 0.71 to 1.28 | 0.87 | 0.46 to 1.63 | |||
2-df test | 0.62 | 0.84 | ||||||||
per allele | 1.03 | 0.94 to 1.12 | 0.56 | 0.94 | 0.77 to 1.15 | 0.56 | ||||
12q24 - rs1292011
| ||||||||||
BRCA1
| AA | 997 (34.1) | 1,321 (35.4) | 305 (34.9) | 1 | 1 | ||||
AG | 1,406 (48.2) | 1,765 (47.3) | 429 (49.1) | 1.00 | 0.90 to 1.10 | 1.11 | 0.93 to 1.31 | |||
GG | 517 (17.7) | 645 (17.3) | 140 (16.0) | 1.01 | 0.89 to 1.15 | 0.98 | 0.78 to 1.24 | |||
2-df test | 0.97 | 0.39 | ||||||||
per allele | 1.00 | 0.94 to 1.07 | 0.91 | 1.01 | 0.91 to 1.13 | 0.82 | ||||
BRCA2
| AA | 715 (35.0) | 907 (35.9) | 110 (36.5) | 1 | 1 | ||||
AG | 961 (47.0) | 1222 (48.4) | 137 (45.5) | 1.02 | 0.90 to 1.15 | 0.94 | 0.71 to 1.25 | |||
GG | 370 (18.1) | 396 (15.7) | 54 (17.9) |
0.83
|
0.70 to 0.97
| 0.89 | 0.61 to 1.28 | |||
2-df test |
0.03
| 0.80 | ||||||||
per allele | 0.93 | 0.86 to 1.00 | 0.07 | 0.94 | 0.78 to 1.13 | 0.51 | ||||
PTHLH - rs10771399
| ||||||||||
BRCA1
| AA | 3,810 (79.8) | 5,179 (81.9) | 1,145 (78.4) | 1 | 1 | ||||
AG | 909 (19.0) | 1078 (17.1) | 289 (19.8) | 0.89 | 0.81 to 0.97 | 1.09 | 0.93 to 1.26 | |||
GG | 56 (1.2) | 65 (1.0) | 27 (1.9) |
0.86
|
0.63 to 1.16
|
1.67
|
1.05 to 2.64
| |||
2-df test |
0.02
| 0.06 | ||||||||
per allele |
0.90
|
0.83 to 0.97
|
6.4 × 10
-3
| 1.14 | 1.00 to 1.30 | 0.06 | ||||
BRCA2
| AA | 2,289 (79.7) | 3,076 (81.2) | 369 (81.5) | 1 | 1 | ||||
AG | 545 (19.0) | 678 (17.9) | 76 (16.8) | 0.94 | 0.84 to 1.06 | 0.88 | 0.67 to 1.16 | |||
GG | 37 (1.3) | 34 (0.9) | 8 (1.8) | 0.79 | 0.49 to 1.26 | 1.48 | 0.63 to 3.46 | |||
2-df test | 0.38 | 0.43 | ||||||||
per allele | 0.93 | 0.84 to 1.04 | 0.19 | 0.96 | 0.75 to 1.23 | 0.75 | ||||
9q31.2 - rs865686
| ||||||||||
BRCA1
| TT | 1,935 (40.5) | 2,621 (41.5) | 605 (41.3) | 1 | 1 | ||||
TG | 2,206 (46.2) | 2,825 (44.7) | 690 (47.1) | 0.94 | 0.88 to 1.01 | 0.99 | 0.87 to 1.12 | |||
GG | 633 (13.3) | 877 (13.9) | 169 (11.5) | 1.03 | 0.93 to 1.15 | 0.85 | 0.70 to 1.03 | |||
2-df test | 0.12 | 0.23 | ||||||||
per allele | 1.00 | 0.95 to 1.05 | 0.88 | 0.94 | 0.86 to 1.03 | 0.17 | ||||
BRCA2
| TT | 1,103 (38.4) | 1,576 (41.6) | 179 (39.6) | 1 | 1 | ||||
TG | 1400 (48.8) | 1712 (45.2) | 215 (47.6) |
0.85
|
0.77 to 0.94
| 0.91 | 0.73 to 1.14 | |||
GG | 367 (12.8) | 501 (13.2) | 58 (12.8) | 0.97 | 0.84 to 1.12 | 0.98 | 0.71 to 1.35 | |||
2-df test |
4.6 × 10
-3
| 0.70 | ||||||||
per allele | 0.94 | 0.88 to 1.01 | 0.10 | 0.97 | 0.83 to 1.13 | 0.67 |
Associations with cancer risk for BRCA2 mutation carriers
Associations by tumour ER-status
ER-positive | ER-negative | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Unaffected N | ER-positive N | ER-negative N | ER status unknown N | HR | 95% CI | P-value | HR | 95% CI | P-value | P-dif | |
CDK2NA/B - rs1011970
| |||||||||||
BRCA1
| 4,893 | 559 | 1,888 | 2,841 | 0.95 | 0.81 to 1.12 | 0.56 | 1.03 | 0.95 to 1.11 | 0.47 | 0.41 |
BRCA2
| 2,928 | 1,372 | 424 | 1,649 |
1.10
|
1.00 to 1.22
|
0.05
| 1.15 | 0.96 to 1.37 | 0.12 | 0.70 |
ZNF365 - rs10995190
| |||||||||||
BRCA1
| 4,895 | 559 | 1,887 | 2,843 | 0.88 | 0.74 to 1.04 | 0.14 | 1.01 | 0.94 to 1.10 | 0.75 | 0.16 |
BRCA2
| 2,927 | 1,370 | 406 | 1,648 |
0.89
|
0.80 to 1.00
|
0.043
| 0.87 | 0.71 to 1.07 | 0.19 | 0.84 |
ZMIZ1 - rs704010
| |||||||||||
BRCA1
| 4,842 | 548 | 1,846 | 2,811 |
1.12
|
1.00 to 1.26
|
0.046
| 1.00 | 0.94 to 1.06 | 0.91 | 0.08 |
BRCA2
| 2,887 | 1,347 | 401 | 1,636 | 1.01 | 0.93 to 1.09 | 0.91 | 1.00 | 0.87 to 1.14 | 0.95 | 0.91 |
10p15 - rs2380205
| |||||||||||
BRCA1
| 4,465 | 540 | 1,812 | 2,513 | 0.90 | 0.80 to 1.01 | 0.08 | 1.02 | 0.96 to 1.09 | 0.46 | 0.06 |
BRCA2
| 2,701 | 1,341 | 396 | 1,543 | 1.02 | 0.95 to 1.10 | 0.60 | 0.94 | 0.82 to 1.08 | 0.39 | 0.31 |
11q13 - rs614367
| |||||||||||
BRCA1
| 4,879 | 557 | 1,886 | 2,832 | 1.09 | 0.93 to 1.29 | 0.30 | 1.04 | 0.96 to 1.12 | 0.40 | 0.59 |
BRCA2
| 2,921 | 1,365 | 405 | 1,639 | 1.06 | 0.96 to 1.17 | 0.26 | 0.84 | 0.69 to 1.04 | 0.10 | 0.05 |
12q24 - rs1292011
| |||||||||||
BRCA1
| 3,429 | 308 | 1,043 | 2,031 | 0.87 | 0.74 to 1.02 | 0.09 | 1.05 | 0.98 to 1.13 | 0.12 |
0.046
|
BRCA2
| 2,065 | 813 | 239 | 1,170 | 0.95 | 0.86 to 1.04 | 0.28 | 0.98 | 0.82 to 1.16 | 0.78 | 0.79 |
PTHLH - rs10771399
| |||||||||||
BRCA1
| 4,889 | 557 | 1,887 | 2,842 | 0.94 | 0.78 to 1.13 | 0.52 |
0.81
|
0.74 to 0.90
|
3.8 × 10
-5
| 0.20 |
BRCA2
| 2,926 | 1,366 | 406 | 1,648 | 0.97 | 0.86 to 1.10 | 0.68 |
0.78
|
0.62 to 1.00
|
0.049
| 0.12 |
9q31.2 - rs865686
| |||||||||||
BRCA1
| 4,892 | 559 | 1,888 | 2,836 | 0.92 | 0.81 to 1.03 | 0.15 | 1.01 | 0.95 to 1.08 | 0.68 | 0.16 |
BRCA2
| 2,924 | 1,370 | 405 | 1,645 |
0.91
|
0.84 to 0.99
|
0.028
| 1.07 | 0.92 to 1.25 | 0.40 | 0.08 |