Table 1.
Prevalence of heterozygous loss-of-function germline mutations in the BRIP1 gene in control cohorts and BC/OC index patients according to tumour site, family history, and age at first diagnosis
| Study sample | n | Negative | Positive (%) | OR | 95% CI | P valuea | Mean AAD (range) |
|---|---|---|---|---|---|---|---|
| ExAC control database | 27,173 | 27,135 | 38 (0.14) | – | – | – | – |
| FLOSSIES control database | 7325 | 7316 | 9 (0.12) | – | – | – | – |
| Geographically matched controls | 2189 | 2186 | 3 (0.14) | – | – | – | – |
| All controls | 36,687 | 36,637 | 50 (0.14) | – | – | – | – |
| OC index patients | 706 | 688 | 18 (2.55) | 19.17 | 11.13–33.03 | <0.0001 | 54 (20–93)b |
| Affected by OC only | 523 | 507 | 16 (3.06) | 23.12 | 13.08–40.88 | < 0.0001 | 53 (20–93)c |
| Affected by OC and BC | 183 | 181 | 2 (1.09) | 8.10 | 1.96–33.53 | 0.0276 | 60 (26–83)d |
| AAD OC < 51 years | 246 | 244 | 2 (0.81) | 6.01 | 1.45–24.82 | 0.0471 | 39 (20–50) |
| AAD OC < 61 years | 425 | 417 | 8 (1.88) | 14.06 | 6.62–29.84 | < 0.0001 | 46 (20–60) |
| AAD OC ≥ 61 years | 255 | 245 | 10 (3.92) | 29.91 | 14.99–59.66 | < 0.0001 | 69 (60–93) |
| Familial OC index cases, overall | 611 | 594 | 17 (2.78) | 20.97 | 12.02–36.57 | < 0.0001 | 54 (20–93)e |
| Familial OC index cases, relative(s) with BC only | 421 | 412 | 9 (2.14) | 16.01 | 7.82–23.76 | < 0.0001 | 53 (20–85)f |
| Familial OC index cases, relative(s) with OC | 190 | 182 | 8 (4.21) | 32.21 | 15.06–68.90 | < 0.0001 | 54 (21–93)g |
| BC index patients | 6341 | 6325 | 16 (0.25) | 1.85 | 1.06–3.26 | 0.0363 | 47 (17–92) |
| AAD BC < 51 years | 4417 | 4407 | 10 (0.23) | 1.66 | 0.84–3.28 | 0.1424 | 41 (17–50) |
| AAD BC < 61 years | 5627 | 5612 | 15 (0.27) | 1.96 | 1.10–3.49 | 0.0272 | 44 (17–60) |
| AAD BC ≥ 61 years | 714 | 713 | 1 (0.14) | 1.03 | 0.14–7.45 | 0.6260 | 68 (61–92) |
| Familial BC index cases, overall | 5668 | 5654 | 14 (0.25) | 1.81 | 1.00–3.30 | 0.0623 | 48 (17–92) |
| Familial BC index patients, relative(s) with BC onlyh | 4641 | 4632 | 9 (0.19) | 1.42 | 0.70–2.90 | 0.3030 | 48 (17–92) |
| Familial BC index patients, relative(s) with OCi | 1027 | 1022 | 5 (0.49) | 3.59 | 1.43–9.01 | 0.0168 | 50 (17–92) |
Univariate logistic regression was performed to estimate odds ratios (OR) and 95% confidence interval (CI)
AAD age at first diagnosis, BC breast cancer, ExAC Exome Aggregation Consortium, OC ovarian cancer
aFisher’s exact test
b–gMean AAD and range refers to a subgroup of 680 patients (b), 511 patients (c), 169 patients (d), 593 patients (e), 410 patients (f), and 183 patients (g)
h2238 BC index patients had one relative with BC and 2403 BC index patients had at least two relatives with BC
i All BC index patients reported at least one relative with OC. In addition, 382 BC index patients had no relatives with BC, 282 BC index cases described one relative with BC, and 363 BC index patients two relatives with BC