Table 3.
Age-specific hazard ratio estimates for the PRS associations and HR estimates for a PRS x age interaction*
Age category, y |
BRCA1 carriers |
BRCA2 carriers |
||||
---|---|---|---|---|---|---|
No. of events | HR per unit SD increase in the ER- PRS (95% CI) | P† | No. of events | HR per unit SD increase in the overall BC PRS (95% CI) | P† | |
Outcome: breast cancer | ||||||
18–39 | 4125 | 1.63 (1.52 to 1.74) | – | 1731 | 1.65 (1.44 to 1.88) | – |
40–49 | 2557 | 1.18 (1.13 to 1.23) | 4.2 × 10−15 | 1587 | 1.22 (1.14 to 1.31) | 8.5 × 10−5 |
50–59 | 846 | 1.14 (1.09 to 1.21) | .40 | 718 | 1.10 (1.02 to 1.19) | .05 |
≥60 | 269 | 1.20 (1.11 to 1.29) | .33 | 294 | 1.12 (1.03 to 1.23) | .75 |
Interaction HR | 0.993 (0.990 to 0.996) | 3.3 × 10−6 | 0.995 (0.991 to 0.999) | .01 | ||
Main effect PRS | 1.69 (1.50 to 1.91) | 1.55 (1.29 to 1.87) | ||||
Outcome: ovarian cancer | ||||||
18–49 | 1258 | 1.55 (1.42 to 1.69) | 172 | 3.05 (2.35 to 3.97) | ||
50–59 | 808 | 1.11 (1.05 to 1.18) | 1.1 × 10−9 | 227 | 1.52 (1.26 to 1.84) | 8.2 × 10−6 |
≥60 | 396 | 1.14 (1.06 to 1.21) | .67 | 232 | 1.21 (1.12 to 1.30) | .03 |
Interaction HR | 0.992 (0.988 to 0.998) | .003 | 0.991 (0.979 to 1.00) | .11 | ||
Main effect PRS | 1.83 (1.43 to 2.34) | 2.48 (1.34 to 4.58) |
The population-derived polygenic risk score (PRS) for estrogen receptor–negative breast cancer was used for the associations with breast cancer in BRCA1 carriers and the overall breast cancer PRS in BRCA2 carriers. P values relate to the difference in PRS association between each age group from the preceding younger group and to the interaction term. CI = confidence interval; HR = hazard ratio; PRS = polygenic risk score.
P value for a two-sided test using a weighted cohort Cox regression with time to breast or ovarian cancer diagnosis, respectively, as the outcome.