Table 2.
Associations between Pathogenic Variants in Established Breast Cancer–Predisposition Genes and Risk of Breast Cancer.*
| Breast Cancer–Predisposition Gene1,2,7 | Case Patients (N = 32,247) | Controls (N = 32,544) | Odds Ratio (95% CI)† | P Value |
|---|---|---|---|---|
| no. with pathogenic variant (%) | ||||
| ATM | 253 (0.78) | 134 (0.41) | 1.82 (1.46–2.27) | <0.001 |
| BARD1 | 49 (0.15) | 35 (0.11) | 1.37 (0.87–2.16) | 0.18 |
| BRCA1 | 275 (0.85) | 37 (0.11) | 7.62 (5.33–11.27) | <0.001 |
| BRCA2 | 417 (1.29) | 78 (0.24) | 5.23 (4.09–6.77) | <0.001 |
| CDH1 | 17 (0.05) | 6 (0.02) | 2.50 (1.01–7.07) | 0.06 |
| CHEK2 | 349 (1.08) | 138 (0.42) | 2.47 (2.02–3.05) | <0.001 |
| NF1‡ | 19 (0.06) | 11 (0.03) | 1.93 (0.91–4.31) | 0.09 |
| PALB2 | 148 (0.46) | 38 (0.12) | 3.83 (2.68–5.63) | <0.001 |
| PTEN | 8 (0.02) | 3 (0.01) | NA | NA |
| RAD51C | 41 (0.13) | 35 (0.11) | 1.20 (0.75–1.93) | 0.44 |
| RAD51D | 26 (0.08) | 14 (0.04) | 1.72 (0.88–3.51) | 0.12 |
| TP53‡ | 19 (0.06) | 2 (0.01) | NA | NA |
| Total | 1621 (5.03) | 531 (1.63) | — | — |
*
The studies in the CARRIERS consortium that were included in this population-based analysis were BWHS, CPSII, CPS3, CTS, MCBCS, MEC, MMHS, NHS, NHSII, WCHS, WHI, and WWHS. NA denotes not applicable (too few events [<5] to calculate a stable odds ratio).
†
Odds ratio estimates for any breast cancer were adjusted for study, age, family history of breast cancer, and race or ethnic group.
‡
Pathogenic variants in NF1 and TP53 were restricted to those with an alternate allele fraction (calculated as the number of alternate allele reads divided by the total number of reads at a specific genomic position) between 0.3 and 0.7.