Table 1.
Parameters used to include the effects of rare high-risk and intermediate-risk pathogenic variants in the models
| Gene | Allele Freq | SS | RR of female breast cancer (95% CI) | RR of EOC (95% CI) | RR of male breast cancer (95% CI) | RR of Prostate cancer | RR of pancreatic cancer (95% CI) | |||||
| BRCA1 | BOADICEA | 0.89 | 1 | age<20 | 1 | age<30 | 8 | |||||
| 0.0006394 | exp (3.0146+0.02412× age) | 20≤age≤29 | exp (−3.55+0.1986× age) | 30≤age≤39 | 1.82 | age<65 | 3.10 | age<65 | ||||
| exp (6.0707−0.07775×age) | 30≤age≤39 | exp (7.1776−0.06959×age) | 40≤age≤49 | 0.84 | age≥65 | 1.54 | age≥65 | |||||
| EOC model | exp (4.2511−0.03226×age) | 40≤age≤49 | exp (4.5236−0.01651×age) | 50≤age≤79 | ||||||||
| 0.0007947 | exp (4.2086−0.03141×age) | 50≤age≤79 | ||||||||||
| BRCA2 | BOADICEA | 0.96 | 1 | age<20 | 1 | age<40 | 80 | 7.33 | age<65 | 5.54 | age<65 | |
| 0.00102 | exp (3.2153−0.008815×age) | 20≤age≤29 | exp (−9.708+0.2427× age) | 40≤age≤53 | 3.39 | age≥65 | 1.61 | age≥65 | ||||
| exp (4.28945−0.04462×age) | 30≤age≤39 | exp (6.50334−0.05751×age) | 54≤age≤57 | |||||||||
| EOC model | exp (3.96865−0.0366×age) | 40≤age≤49 | exp (11.3175−0.140513×age) | 58≤age≤69 | ||||||||
| 0.002576 | exp (1.8169+0.006435× age) | 50≤age≤59 | 4.4 | 70≤age≤79 | ||||||||
| exp (−0.2606+0.04106× age) | 60≤age≤69 | |||||||||||
| 13.0991 | 70≤age≤79 | |||||||||||
| PALB2 | 0.00064 | 0.92 | 1 | age<20 | 1 | age<30 | 1 | age<30 | 1 | 1 | age<30 | |
| 9.1 | 20≤age≤24 | 2.91 (1.40 to 6.04) | age≥30 | 7.34 (1.28 to 42.18) | age≥30 | 2.37 (1.24 to 4.50) | age≥30 | |||||
| 8.97 | 25≤age≤29 | |||||||||||
| 8.85 | 30≤age≤34 | |||||||||||
| 8.54 | 35≤age≤39 | |||||||||||
| 8.02 | 40≤age≤44 | |||||||||||
| 7.31 | 45≤age≤49 | |||||||||||
| 6.55 | 50≤age≤54 | |||||||||||
| 5.92 | 55≤age≤59 | |||||||||||
| 5.45 | 60≤age≤64 | |||||||||||
| 5.1 | 65≤age≤69 | |||||||||||
| 4.82 | 70≤age≤74 | |||||||||||
| 4.56 | 75≤age≤79 | |||||||||||
| CHEK2 | 0.00373 | 0.98 | 1 | age<20 | 1 | 1 | 1 | 1 | ||||
| exp (1.6053−0.01483×age) | age≥20 | |||||||||||
| ATM | 0.0018 | 0.94 | 2.10 (1.17 to 2.57) | 1 | 1 | 1 | 1 | |||||
| BARD1 | 0.00043 | 0.89 | 2.09 (1.35 to 3.23) | 1 | 1 | 1 | 1 | |||||
| RAD51C | 0.00035 | 0.78 | 1.97 (1.48 to 2.62) | 1 | age<30 | 1 | 1 | 1 | ||||
| exp (−1.7974+0.07631× age) | 30≤age<60 | |||||||||||
| exp (9.7592−0.1163×age) | age≥60 | |||||||||||
| RAD51D | 0.00035 | 0.86 | 1.82 (1.34 to 2.47) | 1 | age<30 | 1 | 1 | 1 | ||||
| exp (−2.88662+0.09656× age) | 30≤age<58 | |||||||||||
| exp (5.99144−0.05651×age) | age≥58 | |||||||||||
| BRIP1 | 0.00071 | 0.95 | 1 | 3.41 (2.12 to 5.54) | 1 | 1 | 1 | |||||
'Allele freq’ is the pathogenic variant allele frequency in the general population. RR is relative to the general population. The BOADICEA model includes the effects of BRCA1, BRCA2, PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D, while the EOC model includes the effects of BRCA1, BRCA2, RAD51D, RAD51C, BRIP1 and PALB2. The updated parameters are the allele frequencies for PALB2, CHEK2, ATM, RAD51C, RAD51D, BRAD1 and BRIP1,15 the SS for pathogenic variants for all genes,15 the RR for female breast cancer for ATM, BARD1, RAD51C and RAD51D,15 24 and the EOC, male breast cancer and the pancreatic cancer RRs for PALB2.17 All other parameters are as previously published.8–11 21
BOADICEA, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm; EOC, epithelial tubo-ovarian cancer; RR, relative risk; SS, screening sensitivity.